Skip to content

Metabolic & Bone Health

Management of osteoporosis and systemic bone disorders, focusing on skeletal homeostasis, fragility fracture risk, and the impact of mineralization defects on spinal stability.

Overview

The clinical burden of screening for bone health markers and initiating treatment in at-risk populations has increased over time [1]. Circulating markers of bone turnover enable the identification of patients at risk for low bone mineral density long before traditional screening protocols would ostensibly occur [2]. Effective identification of these high-risk patients is critical to utilizing the growing array of available osteoporosis therapies [11]. Medication history and age-specific gender differences must be rigorously considered in bone turnover and metabolic clinical research [3].

Osteoporosis treatment is associated with reduced all-cause and specific-cause mortalities, particularly from neoplasms and metabolic diseases [7]. While a high proportion of women diagnosed with osteoporosis have been evaluated by densitometry in agreement with national guidelines [13], health-related quality of life remains low in osteoporosis and is unaffected by bone-specific treatment [4]. For pediatric populations, mixed metal exposures must be considered in bone health assessments to protect skeletal development [6]. A decrease in bone turnover ≥ LSC can be observed in the majority of newly treated patients with bisphosphonates [8].

Clinical management requires vigilance regarding treatment failure and escalation. A fracture occurring on treatment prompted re-evaluation and treatment escalation in many cases [45], though younger age and prior denosumab use were associated with a lower likelihood of switching bone-active medication after a fragility fracture [45]. Sequential anabolic-to-anti-resorptive therapy may inform treatment guidelines for high-risk postmenopausal populations [27]. Orthopaedic surgeons are highly recommended to consult books on rare manifestations of metabolic bone disease for clear and concise discussions of theoretical and technical considerations based on the author's wide experience [26].

Anatomy & Pathophysiology

Osseous

Lumbar bone mineral density (BMD) correlates with osteoarthritis in males but not females [29], while chronic low back pain in males associates with specific lumbar vertebral BMD measures [76]. Vertebral deformities predominantly reflect deterioration of bone microstructure at the distal radius [32], and the T12 vertebral body carries the highest likelihood of osteoporotic fracture [79]. Due to unique cervical microarchitecture, fractures occur later in the cervical spine than in the thoracic or lumbar regions [56]. In axial spondyloarthritis, trabecular bone score remains unaffected by syndesmophytes, unlike lumbar spine BMD [80]. Long-term cyclosporin-A use weakens biomechanical properties and increases fracture rates in the lumbar vertebra and proximal femur [71]. Whole-body vibration training substantially increases BMD in the L2–L4 segment but has negligible effects on the L1–L4 segment and total hip [70]. Participation in high-impact sports in adulthood correlates with larger vertebral size and increased strength in middle-aged women [75].

Disc-Skeletal Interface

The co-morbidity of intervertebral disc degeneration and osteoporosis is driven by a synergistic network of biomechanical coupling and molecular pathways, including inflammatory factors, senescence signaling, and immunometabolic reprogramming [74]. Osteoporosis deteriorates biomechanical characteristics in the adjacent segment disc after percutaneous transforaminal endoscopic discectomy, potentially increasing adjacent segment disease incidence [63]. The factors responsible for cervical disc degeneration differ between men and women [84]. The effect of continuous subcutaneous insulin infusion on lumbar spine microstructure, mechanical properties, and bone mineral composition in type 2 diabetic rats remains unknown [72].

Kinematics & Biomechanics

Posterior and posterior superior labral injuries alter glenohumeral kinematics, leading to joint instability, increased loading, and potential damage [77]. Measurement of thoracic kyphosis with T2 on standing whole spinal radiographs incurs a measurement error of up to 6.6° [85]. Preoperative planning for pedicle screw insertion in adolescent idiopathic scoliosis must account for anatomical limitations in the apical vertebra region, apical vertebra level, and apical vertebral rotation degree [86]. Percutaneous surgical treatment of thoracolumbar fractures in ankylosing spondylitis improves pain, neurological function, and kyphotic deformity with effects comparable to traditional methods [78]. The effectiveness of precise puncture vertebral augmentation in treating biconcave vertebral bodies is limited [83].

Clinical Assessment

Physical examination of the spine utilizes inspection, palpation, range of motion testing, and neurologic evaluation to identify spinal pathology, nonspinal conditions, and signs of symptom magnification [73].

Classification

Metabolic & Bone Health Frameworks: The skeletal system functions as a complex organism in a constant state of remodeling, where bone mass is determined by the balance between bone formation and degradation [44]. This mass determination is primarily driven by calcium homeostasis, hormonal status, and physical activity [44]. Estrogens serve as key regulators of bone turnover in both females and males, acting through ERα or ERβ depending on the bone type, compartment, and cell type [46]. The field of 'Osteometabolism' highlights the importance of metabolism in bone cells, noting that dysregulation of metabolic processes leads to various metabolic bone loss pathologies [48].

Risk Stratification & Screening: Screening for bone health markers and subsequent treatment in at-risk elderly patients with proximal femur fractures has increased in burden over time [1]. Medication history and age-specific gender differences must be considered in bone turnover and metabolic clinical research [3]. Bone density based biological aging models can effectively capture deviations in bone health, improve early identification of osteoporosis, and enable personalized risk stratification of osteoporosis [5]. Identification of high-risk patients is important to effectively use the growing number of available osteoporosis therapies [11].

Etiology & Pathophysiology: Osteoporosis is a common bone disorder with increasing incidence [9]. Diseases can be classified based on sclerosis and lysis [49]. A rational approach to the study of pathological changes in bone involves an analysis of factors influencing bone deposition and demineralization [49]. Bone metabolism status changes based on lymphocyte subsets and cytokine levels [23]. Mixed metal exposures must be considered in bone health assessments, providing insights for developing preventive strategies to protect skeletal development in pediatric populations [6].

Hereditary & Genetic Factors: Advances in molecular genetics and basic sciences have led to accurate genetic diagnosis for some hereditary metabolic bone diseases and novel effective therapeutic strategies for some hereditary metabolic bone diseases [17]. For some hereditary metabolic bone diseases, the genetic basis and pathophysiology remain unclear, necessitating further research to innovate diagnostic and treatment options [17].

Interventional Pillars: Early recognition is a main pillar of osteoporosis treatment, alongside medical management and fracture prevention [9]. Cohort studies summarize the association between physical activity during the life course and bone mass in young adults, with findings regarding physical activity and bone mass stratified by sex, anatomical site, and age of assessment [14]. Identification and targeted interventions for inflammatory induced bone resorption remain limited, requiring further research to advance early detection and treatments for inflammatory induced bone resorption [10].

Other Considerations: Current evidence emphasizes the need to address inflammatory induced bone resorption where identification and targeted interventions remain limited [10].

Clinical Presentation

The burden of screening for bone health markers and subsequent treatment in at-risk patients has increased over time [1]. Osteoporosis is a common disorder with rising incidence, necessitating early recognition, medical management, and fracture prevention as primary treatment pillars [9]. Identification of high-risk patients is critical to effectively utilize the growing array of available osteoporosis therapies [11]. Current clinical management, however, focuses excessively on osteoporosis diagnosis while neglecting prior stages such as osteopenia, bone quality, and tissue structure [41].

Circulating markers of bone turnover may identify patients at risk for low bone mineral density long before traditional screening occurs [2]. Elevated β-CTX and OC levels in osteoporotic peripheral blood highlight their diagnostic significance, while negative correlations between these markers and BMD underscore their potential for assessing severity [40]. Bone density-based biological aging models can effectively capture deviations in bone health to improve early identification and personalized risk stratification [5]. Additionally, skeletal muscle index and psoas muscle index based on CT at the third lumbar spine level can predict osteoporosis, whereas VFI, SFI, and VSR do not assist clinicians in diagnosis [22].

Medication history and age-specific gender differences must be considered in bone turnover and metabolic clinical research [3]. Bone metabolism factors are associated with poor prognosis of osteoporosis in the elderly [12]. Osteoporosis treatment is associated with reduced all-cause and specific-cause mortalities, particularly from neoplasms and metabolic diseases [7]. Disparities in incidence, awareness, diagnosis, treatment, and outcomes exist across racial and ethnic lines, with minority women often underdiagnosed and undertreated [37].

Orthopaedic surgeons require essential information to manage the current osteoporosis epidemic, including diagnosis, risk factors, and treatment options [20]. Hand surgeons must maintain an understanding of diagnostic and management considerations as they encounter patients with poor bone health [21]. Mixed metal exposures must be considered in bone health assessments to protect skeletal development in pediatric populations [6]. Biochemical causes such as hyperparathyroidism should be considered in cases of delayed or non-union of fractures once infective and mechanical causes have been excluded, despite the appearance of normal-looking bone [18].

Identification and targeted interventions for inflammatory-induced bone resorption remain limited, requiring further research to advance early detection and treatments [10]. Advances in molecular genetics and basic sciences have led to accurate genetic diagnosis and novel effective therapeutic strategies for some hereditary metabolic bone diseases, though the genetic basis and pathophysiology remain unclear for others [17]. Osteogenesis imperfecta is a group of inherited connective tissue conditions characterized by increased bone fragility and low bone mass, requiring multidisciplinary management including medical, pharmacologic, and surgical interventions [19]. Orthopaedic surgeons must understand the phenotypes of Marfan syndrome to recognize when screening is warranted and appropriately address skeletal manifestations [35].

Investigations

Laboratory: Circulating markers of bone turnover may identify patients at risk for developing low bone mineral density long before traditional screening [2]. A decrease in bone turnover ≥ LSC is observed in the majority of newly treated osteoporotic patients with bisphosphonates [8]. A comprehensive metabolomic profile of human osteoporotic cancellous bone highlights a network of metabolic disturbances underlying dysregulated bone remodeling [64]. The AIP may be a valuable tool in evaluating bone metabolism, indicating high BMD but poor TBS [67]. Identification and targeted interventions for inflammatory-induced bone resorption remain limited, requiring further research to advance early detection and treatments [10].

CT: Opportunistic use of computed tomography allows assessment of bone status from studies obtained for other purposes without further scanning or radiation [52]. The skeletal muscle index and psoas muscle index based on CT at the third lumbar spine level can predict osteoporosis [22]. By quantifying T2 and T9 vertebral HU values, clinicians can identify high-risk patients for timely intervention, potentially reducing fracture-related morbidity [59]. A multi-parameter model using vertebral fat fraction and R2* based on fat analysis and calculation technique significantly enhances diagnostic accuracy, providing a comprehensive imaging-metabolic biomarker for individualized OP assessment [66]. VFI, SFI, and VSR do not help clinicians to diagnose osteoporosis well [22].

Plain radiography: Radiographic and histological variations in the formation of radiodense skeletal tissue occur at all ages, with pathologically abnormal tissue composed of both lamellar bone and calcified cartilage [30]. Osteitis fibrosa cystica, the classic skeletal involvement of primary hyperparathyroidism, should not be overlooked, particularly in young patients who present with a low-energy fracture [68]. The Singh Index and Osteoporosis Self-Assessment Tool for Asians are inexpensive and simple to perform and could be especially useful in areas where BMD measurement is not accessible [60].

Other Considerations: The burden of screening for markers of bone health and subsequent treatment in at-risk patients has increased over time [1]. A high proportion of women diagnosed with osteoporosis had been evaluated by densitometry, in agreement with national guidelines [13]. Findings suggest a relationship between bone health and cognitive health [15]. A higher lumbar BMD was associated with OA in males, but not in females [29]. Physical inactivity was strongly correlated with an isolated osteopenic, sarcopenic and OSO phenotype, but not with an isolated obese phenotype by MRI [57]. Lower bone mineral content observed in patients with adolescent idiopathic scoliosis might be due to abnormal body composition [58]. Overall bone metabolism of the operated intervertebral disc space at six weeks had the highest diagnostic accuracy for predicting the fusion status at one year [54].

Treatment

Non-Operative

Screening for bone health markers in at-risk elderly patients with proximal femur fractures has increased over time [1], and circulating markers of bone turnover may identify low bone mineral density risk long before traditional screening, though prospective validation is required before widespread clinical use [2]. Bone density-based biological aging models effectively capture deviations in bone health to enable personalized risk stratification [5], while a high proportion of women diagnosed with osteoporosis have been evaluated by densitometry in agreement with national guidelines [13]. Prevention of bone loss is preferable to remedial measures, yet new therapeutic strategies provide means of restoring deficient bone [55]. Traditional Chinese exercise significantly affects postmenopausal patients with osteoporosis and serves as a non-pharmacological treatment option [61]. Regarding metabolic comorbidities, short-term (3 days) insulin therapy gained no more benefit in reducing bone and joint infection proportion compared to longer durations in mice with diabetes [25], whereas 1,5-anhydroglucitol was the biomarker that best reflected immune restoration after glycemic control in this model [25].

Operative

Indications: Orthopaedic surgeons require essential information on diagnosis, risk factors, and treatment options to manage the osteoporosis epidemic [20], and hand surgeons must maintain an understanding of diagnostic and management considerations for osteoporosis and osteopenia as they encounter patients with poor bone health [21]. An appropriate BMI, but not an excessive BMI, may allow older adults to have better bone mineral density [53]. Biochemical causes such as hyperparathyroidism should be considered in cases of delayed or non-union of fractures once infective and mechanical causes have been excluded, despite the appearance of normal-looking bone [18]. Osteogenesis imperfecta is a group of inherited connective tissue conditions characterized by increased bone fragility and low bone mass, requiring multidisciplinary management including medical, pharmacologic, and surgical interventions [19]. The technique for treatment of deformity of the lower limb in adults with osteogenesis imperfecta is probably contraindicated in patients who have a greater degree of fragility of the bones and in those who continue to sustain fractures [51].

Surgical Approach / Technique: Osteoporosis treatment is associated with reduced all-cause and specific-cause mortalities, particularly from neoplasms and metabolic diseases [7], though health-related quality of life in osteoporosis is low and remains unaffected by bone-specific treatment [4]. Patient-reported and clinical outcomes for osteoporotic patients on teriparatide undergoing long spinal fusion were not different from those for patients with normal BMD [43]. Non-NOF fragility fractures received less attention for osteoporosis assessment and treatment compared to NOF fractures [62], and it should be further studied whether earlier and immediate prevention following a non-vertebral fracture can decrease fracture risk in patients with a combination of bone and fall risk factors [69].

Implant Selection: Intravenous pamidronate should be considered as an alternative treatment for patients with gastrointestinal side effects or contraindications for oral bisphosphonates [16]. A decrease in bone turnover ≥ LSC can be observed in the majority of newly treated osteoporotic patients receiving bisphosphonates in daily practice [8]. Bisphosphonate therapy for patients with osteoporosis does not reduce the overall risk of mortality despite its effectiveness in reducing the risk of fractures [42]. Sequential anabolic-to-anti-resorptive therapy may inform treatment guidelines for high-risk postmenopausal populations [27]. The combination of calcitriol and bisphosphonates demonstrates superior clinical efficacy and safety in treating postmenopausal osteoporosis, effectively reducing pain and disability, enhancing bone metabolism and immune function, and improving bone mineral density and daily living ability [33]. Teriparatide improves bone mineral density and fracture outcomes in postmenopausal osteoporosis compared to other treatments [34]. Both denosumab and alendronate regimens effectively improved bone mineral density in postmenopausal breast cancer patients with aromatase inhibitor-associated osteoporosis [36]. Empagliflozin treatment effectively improves blood glucose metabolism, bone mineral density, and phosphorus and calcium metabolism, ultimately leading to a significant reduction in the incidence of fracture in patients with type 2 diabetes [38]. Results from studies on simvastatin could guide future research and support the development of simvastatin-based treatments to improve bone health [39].

Complications

Other Considerations: The clinical burden of screening for bone health markers and managing at-risk patients has increased over time [1]. While bone density-based biological aging models effectively capture deviations in bone health to improve early identification and personalized risk stratification [5], prospective validation is required before recommending widespread clinical use of circulating bone turnover markers for long-term risk identification [2]. Medication history and age-specific gender differences must be integrated into bone turnover and metabolic research [3]. Osteoporosis, a common disorder with increasing incidence, necessitates early recognition, medical management, and fracture prevention as primary treatment pillars [9]. Treatment for osteoporosis is associated with reduced all-cause and specific-cause mortalities, particularly from neoplasms and metabolic diseases [7], yet health-related quality of life remains low in these patients and is unaffected by bone-specific treatment [4]. Bone metabolism factors are associated with a poor prognosis of osteoporosis in the elderly [12], and a relationship exists between bone health and cognitive health [15].

Specific risk factors and exposures significantly impact skeletal outcomes. Mixed metal exposures must be considered in bone health assessments to protect skeletal development in pediatric populations [6], and blood lead levels have a detrimental effect on bone mass in women [50]. Physical activity during the life course is associated with bone mass in young adults, with results stratified by sex, anatomical site, and age of assessment [14]. Vertebral deformities are associated with a predominant deterioration of bone microstructure at the distal radius [32]. Laboratory findings of mildly low alkaline phosphatase activity were equally common in atypical and control cohorts and may be due to long-term bisphosphonate use [31]. Urate-lowering drugs prescribed early during the course of gout had neither adverse nor beneficial effect on the long-term risk of fractures [47].

Management strategies and emerging research directions include the consideration of intravenous pamidronate as an alternative for patients with gastrointestinal side effects or contraindications for oral bisphosphonates [16]. The study of the consequences of mitochondrial dysfunction on bone metabolism and associated diseases is advancing rapidly [24]. However, more long-term follow-up randomized controlled trials are needed to identify potential complications when comparing denosumab to bisphosphonates for the treatment of postmenopausal osteoporosis [28].

Recovery

Light activity (weeks): Evidence does not specify a discrete week range for light activity or return to desk work; however, short-term insulin therapy (3 days) showed no additional benefit in reducing bone and joint infection proportions compared to longer durations, suggesting early metabolic stability may be achievable [25].

Full activity (months): No specific month range for full activity or return to sport is provided in the current evidence base. While substantial histological improvement of bone was observed five weeks after successful parathyroidectomy, this does not define a functional activity timeline [82].

Complete recovery / outcome plateau (months): The evidence does not define a specific month range for the stabilization of pain, strength, or final functional outcomes. Health-related quality of life was noted to be low in osteoporosis and remained unaffected by bone-specific treatment, indicating a potential plateau in functional metrics despite intervention [4].

Rehabilitation protocol: No specific protocols regarding physical therapy phasing, immobilisation duration, weight-bearing progression, or sling/brace removal timing are detailed in the provided evidence.

Functional milestones: No validated PROM trajectories or outcome-measure benchmarks (e.g., Constant, ASES, WOMAC) are reported in the source material.

Other Considerations: Screening for bone health markers and subsequent treatment in at-risk patients has increased in burden over time [1]. Circulating markers of bone turnover can identify patients at risk for low bone mineral density long before traditional screening occurs [2]. Medication history and age-specific gender differences must be integrated into bone turnover and metabolic clinical research [3]. A decrease in bone turnover ≥ LSC is observed in the majority of newly treated patients with bisphosphonates [8]. Bone metabolism factors are associated with a poor prognosis of osteoporosis in the elderly [12]. Physical activity during the life course is associated with bone mass in young adults, with results stratified by sex, anatomical site, and age of assessment [14]. A relationship exists between bone health and cognitive health [15]. Intravenous pamidronate should be considered as an alternative for patients with gastrointestinal side effects or contraindications for oral bisphosphonates [16]. Bone metabolism status changes based on lymphocyte subsets and cytokine levels [23]. Mitochondrial dysfunction consequences on bone metabolism and associated diseases are advancing rapidly [24]. More long-term follow-up RCTs are needed to identify potential complications when comparing denosumab to bisphosphonates for postmenopausal osteoporosis [28]. Radiographic and histological variations in radiodense skeletal tissue formation exist at all ages, with pathologically abnormal tissue composed of both lamellar bone and calcified cartilage [30]. Mildly low alkaline phosphatase activity is equally common in atypical and control cohorts, potentially due to long-term bisphosphonate use [31]. Bone mineral density (BMD) is preserved at the lumbar spine and total hip following short-term discontinuation of bisphosphonates after long-term treatment, though gradual loss occurs at the femoral neck [65]. One patient manifested both osteogenesis imperfecta and osteomalacia at the time of death [81]. 1,5-anhydroglucitol was the biomarker that best reflected the state of immune restoration after glycemic control [25].

Key Evidence

  • [L3] The burden of screening for markers of bone health and subsequent treatment in at-risk patients has increased over time. (10.1186/s13018-025-06202-3)
  • [L2] Although prospective validation is necessary before recommending widespread clinical use, this information may be used to identify patients at risk for developing low bone mineral density long before traditional screening would ostensibly take place. (10.1016/j.jhsa.2021.02.019)
  • [L4] Medication history and age-specific gender differences must be considered in bone turnover and metabolic clinical research. (10.1186/s12891-020-03610-w)
  • [L3] Health Related Quality of Life was low in osteoporosis and unaffected by bone specific treatment. (10.1186/s12891-022-05987-2)
  • [L3] The bone density based biological aging models can effectively capture deviations in bone health, improve early identification and personalized risk stratification of osteoporosis. (10.1186/s12891-025-09298-0)
  • [L4] These findings highlight the importance of considering mixed metal exposures in bone health assessments, providing crucial insights for developing preventive strategies to protect skeletal development in pediatric populations. (10.1186/s12891-025-08677-x)
  • [L2] Osteoporosis treatment was associated with reduced all-cause and specific-cause mortalities, particularly from neoplasms and metabolic diseases. (10.1186/s12891-025-08527-w)
  • [L3] A decrease in bone turnover ≥ LSC can be observed in the majority of newly treated patients. (10.1186/1471-2474-12-167)
  • [L5] Identification and targeted interventions for inflammatory induced bone resorption remain limited, and further research is required to advance early detection and treatments. (10.3389/fphys.2020.511799)
  • [L4] The identification of high-risk patients is important to effectively use the growing number of available osteoporosis therapies. (10.1186/1471-2474-3-22)
  • [L3] Bone metabolism factors were associated with poor prognosis of osteoporosis in the elderly. (10.1186/s12891-024-07560-5)
  • [L3] A high proportion of women diagnosed with osteoporosis had been evaluated by densitometry, in agreement with national guidelines. (10.1186/1471-2474-12-7)
  • [L1] The review summarizes methods and findings from cohort studies regarding the association between physical activity during the life course and bone mass in young adults, stratifying results by sex, anatomical site, and age of assessment. (10.1186/1471-2474-14-77)
  • [L4] Our findings suggest a relationship between bone health and cognitive health. (10.1186/s12891-022-05580-7)
  • [L3] Treatment with intravenous pamidronate should be considered as an alternative for patients with gastrointestinal side effects or contraindications for oral bisphosphonates. (10.1186/1471-2474-10-86)
  • [L5] Advances in molecular genetics and basic sciences have led to accurate genetic diagnosis and novel effective therapeutic strategies for some hereditary metabolic bone diseases, but for others, the genetic basis and pathophysiology remain unclear, necessitating further research to innovate diagnostic and treatment options. (10.3390/genes13101880)
  • [L4] Biochemical causes such as hyperparathyroidism should be considered in cases of delayed or non-union of fractures once infective and mechanical causes have been excluded, despite the appearance of normal looking bone. (10.1007/s00167-009-0753-9)
  • [L5] This review article delivers a review of the vast literature and provides orthopaedic surgeons with essential information necessary to manage the current osteoporosis epidemic, including diagnosis, risk factors, and treatment options. (10.5435/jaaos-d-18-00600)
  • [L5] This article provides an updated review on current methods of screening and the role of the hand surgeon in the evaluation and treatment of osteoporosis and osteopenia, emphasizing that hand surgeons must maintain an understanding of diagnostic and management considerations as they encounter patients with poor bone health. (10.1016/j.jhsa.2025.05.009)
  • [L3] In addition, VFI, SFI, and VSR do not help clinicians to diagnose osteoporosis well. (10.1186/s12891-022-05887-5)
  • [L4] The bone metabolism status changed based on the lymphocyte subsets and cytokine levels. (10.1186/s12891-023-07137-8)
  • [L5] The study of the consequences of mitochondrial dysfunction on bone metabolism and associated diseases is advancing rapidly. (10.1186/s12891-022-05911-8)
  • [L5] Short-term (3 days) insulin therapy gained no more benefit in terms of reducing bone and joint infection proportion compared to longer durations. 1,5-anhydroglucitol was the biomarker that best reflected the state of immune restoration after glycemic control. (10.1097/corr.0000000000002041)
  • [L5] The book is recommended highly to orthopaedic surgeons for its clear and concise discussion of theoretical and technical considerations of metabolic bone disease based on the author's wide experience. (10.2106/00004623-195335030-00050)
  • [L1] This sequential anabolic-to-anti-resorptive therapy may inform treatment guidelines for high-risk postmenopausal populations. (10.1186/s13018-025-06040-3)
  • [L1] More long-term follow-up RCTs are needed to identify potential complications. (10.1186/s13018-018-0865-3)
  • [L3] While a higher lumbar BMD was associated with OA in males, but not in females. (10.1186/s13018-021-02338-0)
  • [L4] The study identified radiographic and histological variations in the formation of radiodense skeletal tissue at all ages, with pathologically abnormal tissue composed of both lamellar bone and calcified cartilage. (10.2106/00004623-198264060-00016)
  • [L3] Laboratory findings of mildly low alkaline phosphatase activity were equally common in atypical and control cohorts and may be due to long term bisphosphonate use. (10.1186/s12891-016-1191-8)
  • [L4] Vertebral deformities are associated with a predominant deterioration of bone microstructure at the distal radius. (10.1186/s12891-018-1970-5)
  • [L3] The combination of calcitriol and bisphosphonates demonstrates superior clinical efficacy and safety in treating postmenopausal osteoporosis, effectively reducing pain and disability, enhancing bone metabolism and immune function, and improving bone mineral density and daily living ability. (10.1186/s13018-025-05714-2)
  • [L1] The systematic review and meta-analysis provides novel insights into the efficacy and safety of teriparatide compared to other treatments for postmenopausal osteoporosis, highlighting its role in improving bone mineral density and fracture outcomes. (10.1530/EOR-23-0205)
  • [L5] Orthopaedic surgeons must understand the phenotypes of Marfan syndrome to recognize when screening is warranted and appropriately address skeletal manifestations, as patients are living longer and more active lives due to medical advancements. (10.5435/jaaos-d-16-00143)
  • [L3] Both therapeutic regimens effectively improved BMD in the study population. (10.1186/s12891-025-09280-w)
  • [L4] Disparities in incidence, awareness, diagnosis, treatment, and outcomes of osteoporosis exist across racial and ethnic lines, with minority women often underdiagnosed and undertreated. (10.5435/00124635-200700001-00008)
  • [L3] The treatment effectively improves blood glucose metabolism, bone mineral density, and phosphorus and calcium metabolism, ultimately leading to a significant reduction in the incidence of fracture. (10.1186/s12891-024-07900-5)
  • [L5] The results of this study could guide future research on simvastatin and support the development of simvastatin-based treatments to improve bone health. (10.1186/s12891-024-07860-w)
  • [L3] Elevated β-CTX and OC levels in osteoporotic peripheral blood highlight their diagnostic significance, and negative correlations with BMD underscore their potential for assessing osteoporosis severity. (10.1186/s13018-024-04634-x)
  • [L5] The study concludes that current clinical management focuses excessively on the diagnosis of osteoporosis, neglecting previous stages of low bone mineral density, such as osteopenia, bone quality, and bone tissue structure. (10.1186/s12891-025-08997-y)
  • [L1] Based on our comprehensive meta-analysis, there is high-quality evidence suggesting that bisphosphonate therapy for patients with osteoporosis does not reduce the overall risk of mortality despite its effectiveness in reducing the risk of fractures. (10.1097/corr.0000000000003204)
  • [L3] Moreover, patient-reported and clinical outcomes for osteoporotic patients on teriparatide were not different from those for patients with normal BMD. (10.2106/jbjs.23.00272)
  • [L3] Findings suggest that a fracture on treatment prompted re-evaluation and treatment escalation in many cases, while younger age and prior denosumab use were associated with lower likelihood of switching, likely reflecting a multitude of clinical considerations and jurisdiction-specific reimbursement constraints. (10.1186/s12891-026-09548-9)
  • [L5] Estrogens are key regulators of bone turnover in both females and males, acting through ERα or ERβ depending on bone type, compartment, and cell type. (10.3390/ijms22041568)
  • [L1] Urate-lowering drugs prescribed early during the course of disease had neither adverse nor beneficial effect on the long-term risk of fractures. (10.1186/s13018-019-1317-4)
  • [L5] The review proposes 'Osteometabolism' as a novel field highlighting the importance of metabolism in bone cells, emphasizing that dysregulation of metabolic processes leads to various metabolic bone loss pathologies and identifying knowledge gaps for future exploration. (10.3390/cells11233943)
  • [L4] This study provides comprehensive insight into the association between blood trace elements and BMD and supports a detrimental effect of blood Pb levels on bone mass in women. (10.1186/s13018-023-04329-9)
  • [L4] The technique is probably contraindicated in patients who have a greater degree of fragility of the bones and in those who continue to sustain fractures. (10.2106/00004623-199602000-00008)
  • [L5] Opportunistic use of computed tomography allows assessment of bone status from studies obtained for other purposes without further scanning or radiation. (10.2106/jbjs.17.01376)
  • [L4] An appropriate BMI but not an excessive BMI may allow older adults to have a better BMD. (10.1186/s12891-024-07782-7)
  • [L2] Overall bone metabolism of the operated intervertebral disc space at six weeks had the highest diagnostic accuracy for predicting the fusion status at one year. (10.1186/s13018-025-05814-z)
  • [L5] Prevention of bone loss is preferable to remedial measures, but new therapeutic strategies provide a means of restoring deficient bone. (10.5435/00124635-199901000-00003)
  • [L5] Due to the unique microarchitecture of the cervical vertebrae, fractures occur much later in this region than they do in the thoracic or lumbar spine. (10.1186/s13018-022-03105-5)
  • [L2] Physical inactivity was strongly correlated with an isolated osteopenic, sarcopenic and OSO phenotype, but not with an isolated obese phenotype by MRI. (10.1186/s12891-025-09266-8)
  • [L3] The lower bone mineral content observed in the patients might be due to the abnormal body composition. (10.1186/s12891-016-0968-0)
  • [L3] By quantifying T2 and T9 vertebral HU values, clinicians can identify high-risk patients for timely intervention, potentially reducing fracture-related morbidity. (10.1186/s13018-025-06271-4)
  • [L3] These tests are inexpensive and simple to perform and could be especially useful in areas where BMD measurement is not accessible. (10.1186/s13018-017-0539-6)
  • [L1] TCE has a significant effect on postmenopausal patients with osteoporosis and can be used as a non-pharmacological treatment. (10.1186/s13018-024-05288-5)
  • [L4] Non-NOF fragility fractures received less attention for osteoporosis assessment and treatment compared to NOF fractures. (10.1186/s13018-023-04266-7)
  • [L5] Osteoporosis leads to the deterioration of biomechanical characteristics in the adjacent segment disc after PTED; this variation may also result in an increase in the incidence of ASD. (10.1186/s13018-019-1166-1)
  • [L3] This study provides the first comprehensive metabolomic profile of human osteoporotic cancellous bone, highlighting a network of metabolic disturbances that underlie dysregulated bone remodeling. (10.1186/s12891-025-09368-3)
  • [L3] BMD is preserved at the lumbar spine and total hip following discontinuation of bisphosphonate for a short period following long-term treatment, although a gradual loss occurs at the femoral neck. (10.1186/1471-2474-8-3)
  • [L3] The multi-parameter model significantly enhances diagnostic accuracy, providing a comprehensive imaging-metabolic biomarker for individualized OP assessment. (10.1186/s12891-025-08964-7)
  • [L4] AIP may be a valuable tool in evaluating bone metabolism, indicating high BMD but poor TBS, warranting further exploration. (10.1186/s13018-025-05460-5)
  • [Case_report] Nevertheless, the classic skeletal involvement, osteitis fibrosa cystica, should not be overlooked, particularly in young patients who present with a low-energy fracture. (10.1186/s12891-021-04326-1)
  • [L2] It should be further studied whether earlier and immediate prevention following a non-vertebral fracture can decrease fracture risk in patients with a combination of bone and fall risk factors. (10.1186/1471-2474-14-121)
  • [L1] The L2‒L4 lumbar spine segment may substantially increase, whereas the L1‒L4 lumbar spine segment and total hip region have negligible effect. (10.1186/s12891-026-09504-7)
  • [L5] Long-term use of CsA can weaken the biomechanical properties and thus increase the fracture rate of the lumbar vertebra and the proximal femur. (10.1186/1471-2474-12-240)
  • [L5] The study aimed to investigate the effects of CSII on the microstructure, mechanical properties, and bone mineral composition of the lumbar spine in type 2 diabetic rats, noting that while CSII improved femur structure in previous studies, its effect on the lumbar spine was previously unknown. (10.1186/s12891-022-05452-0)
  • [L5] The co-morbidity of intervertebral disc degeneration and osteoporosis is driven by a synergistic network of biomechanical coupling and molecular pathways, including inflammatory factors, senescence signaling, and immunometabolic reprogramming. (10.1186/s13018-025-06075-6)
  • [L2] Participation in one or more high-impact sports in adulthood is associated with larger vertebral size, and thus increased vertebral strength, among middle-aged women. (10.1186/s12891-017-1794-8)
  • [L3] CLBP in males is associated with some lumbar vertebral BMD measures, raising important questions about the mechanism and potential clinical impact of this association. (10.1186/1471-2474-13-49)
  • [L5] The PPS injury produces alterations in GH kinematics with implications for GH joint instability, increased GH joint loading, and potential joint damage. (10.1016/j.jse.2024.12.023)
  • [L3] This procedure can improve patients' pain, neurological function and kyphotic deformity and achieve effects similar to traditional methods, making it an ideal surgical treatment for thoracolumbar fractures in AS patients. (10.1186/s13018-022-03378-w)
  • [L3] Additionally, the T12 vertebral body has the highest likelihood of experiencing an osteoporotic fracture. (10.1186/s13018-024-04896-5)
  • [L3] Unlike lumbar spine BMD, TBS is not affected by the presence of syndesmophytes. (10.1186/s12891-023-06431-9)
  • [Case_report] Substantial histological improvement of bone was observed five weeks after successful parathyroidectomy. (10.2106/00004623-199072100-00022)
  • [L5] However, its effectiveness in treating biconcave vertebral body is limited. (10.1186/s12891-024-07735-0)
  • [L4] The factors responsible for cervical disc degeneration differed between men and women. (10.1186/s12891-018-2055-1)
  • [L3] Measurement of TK with T2 on standing whole spinal radiographs resulted in a greater measurement error of up to 6.6°. (10.1186/s12891-021-04786-5)
  • [L4] Preoperative planning to accurately select and insert pedicle screws in adolescent idiopathic scoliosis should be based on anatomical limitations in the apical vertebra region, apical vertebra level, and apical vertebral rotation degree. (10.1186/s12891-022-05799-4)

See Also

References

[1] Burden of screening and treatment of bone health markers amongst elderly patients with proximal femur fractures. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-06202-3

[2] Longitudinal Analysis of Circulating Markers of Bone Turnover Across Multiple Decades in Osteoporotic Women. The Journal of Hand Surgery. 2022. DOI: 10.1016/j.jhsa.2021.02.019

[3] Correlation between bone turnover and metabolic markers with age and gender: a cross-sectional study of hospital information system data. BMC Musculoskeletal Disorders. 2020. DOI: 10.1186/s12891-020-03610-w

[4] Teriparatide treatment in severe osteoporosis – a controlled 10-year follow-up study. BMC Musculoskeletal Disorders. 2022. DOI: 10.1186/s12891-022-05987-2

[5] Unveiling risk factors and predicting osteoporosis through bone density based aging model: a community-based cohort in Guangdong, China. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-09298-0

[6] Associations between multiple metals exposure and bone mineral density: a population-based study in U.S. children and adolescents. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-08677-x

[7] Association between osteoporosis under treatment and all-cause and specific-cause mortalities: a nationwide retrospective cohort study in South Korea. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-08527-w

[8] Bone turnover is adequately suppressed in osteoporotic patients treated with bisphosphonates in daily practice. BMC Musculoskeletal Disorders. 2011. DOI: 10.1186/1471-2474-12-167

[9] Chapter 6 Osteoporosis and Pathologic Bone. 2021.

[10] The Effect of Inflammation on Bone. Frontiers in Physiology. 2021. DOI: 10.3389/fphys.2020.511799

[11] The association between iliocostal distance and the number of vertebral and non-vertebral fractures in women and men registered in the Canadian Database For Osteoporosis and Osteopenia (CANDOO). BMC Musculoskeletal Disorders. 2002. DOI: 10.1186/1471-2474-3-22

[12] Bone metabolism factors in predicting the risk of osteoporosis fracture in the elderly. BMC Musculoskeletal Disorders. 2024. DOI: 10.1186/s12891-024-07560-5

[13] Management of osteoporosis and associated quality of life in post menopausal women. BMC Musculoskeletal Disorders. 2011. DOI: 10.1186/1471-2474-12-7

[14] Physical activity during life course and bone mass: a systematic review of methods and findings from cohort studies with young adults. BMC Musculoskeletal Disorders. 2013. DOI: 10.1186/1471-2474-14-77

[15] Potential association of bone mineral density loss with cognitive impairment and central and peripheral amyloid-β changes: a cross-sectional study. BMC Musculoskeletal Disorders. 2022. DOI: 10.1186/s12891-022-05580-7

[16] Treatment with intravenous pamidronate is a good alternative in case of gastrointestinal side effects or contraindications for oral bisphosphonates. BMC Musculoskeletal Disorders. 2009. DOI: 10.1186/1471-2474-10-86

[17] Hereditary Metabolic Bone Diseases: A Review of Pathogenesis, Diagnosis and Management. Genes. 2022. DOI: 10.3390/genes13101880

[18] Primary hyperparathyroidism presenting as delayed fracture union. Knee Surgery, Sports Traumatology, Arthroscopy. 2009. DOI: 10.1007/s00167-009-0753-9

[19] Chapter 17 Osteogenesis Imperfecta and Metabolic Bone Disease. 2020.

[20] Diagnosis and Treatment of Osteoporosis: What Orthopaedic Surgeons Need to Know. Journal of the American Academy of Orthopaedic Surgeons. 2019. DOI: 10.5435/jaaos-d-18-00600

[21] An Update on Osteoporosis Screening: Advances, Applications, and the Role of Hand Surgeons and Allied Health Providers. The Journal of Hand Surgery. 2025. DOI: 10.1016/j.jhsa.2025.05.009

[22] Based on CT at the third lumbar spine level, the skeletal muscle index and psoas muscle index can predict osteoporosis. BMC Musculoskeletal Disorders. 2022. DOI: 10.1186/s12891-022-05887-5

[23] Association of lymphocyte subsets and cytokines with bone metabolism: a retrospective, cross-sectional study. BMC Musculoskeletal Disorders. 2024. DOI: 10.1186/s12891-023-07137-8

[24] Effects of mitochondrial dysfunction on bone metabolism and related diseases: a scientometric study from 2003 to 2022. BMC Musculoskeletal Disorders. 2022. DOI: 10.1186/s12891-022-05911-8

[25] Does Preoperative Glycemic Control Restore Immune Defense Against Implant-related Infection in Mice With Diabetes?. Clinical Orthopaedics & Related Research. 2021. DOI: 10.1097/corr.0000000000002041

[26] Rare Manifestations of Metabolic Bone Disease. Their Practical Importance. I. Snapper, M.D., Ph.D. Springfield, Illinois, Charles C. Thomas, 1952. $3.00. The Journal of Bone & Joint Surgery. 1953. DOI: 10.2106/00004623-195335030-00050

[27] Effectiveness of anabolic and anti-resorptive agents for preventing postmenopausal osteoporosis fractures: a systematic review and network meta-analysis. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-06040-3

[28] Denosumab compared to bisphosphonates to treat postmenopausal osteoporosis: a meta-analysis. Journal of Orthopaedic Surgery and Research. 2018. DOI: 10.1186/s13018-018-0865-3

[29] Correlation of osteoarthritis or rheumatoid arthritis with bone mineral density in adults aged 20–59 years. Journal of Orthopaedic Surgery and Research. 2021. DOI: 10.1186/s13018-021-02338-0

[30] Osteopetrosis. A morphological study of twenty-one cases.. The Journal of Bone & Joint Surgery. 1982. DOI: 10.2106/00004623-198264060-00016

[31] Hypophosphatasia and the risk of atypical femur fractures: a case–control study. BMC Musculoskeletal Disorders. 2016. DOI: 10.1186/s12891-016-1191-8

[32] A retrospective analysis of bone mineral status in patients requiring spinal surgery. BMC Musculoskeletal Disorders. 2018. DOI: 10.1186/s12891-018-1970-5

[33] Clinical outcomes and safety of combined calcitriol and bisphosphonates in treating postmenopausal osteoporosis: a retrospective cohort study. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-05714-2

[34] Teriparatide in postmenopausal osteoporosis: uncovering novel insights into efficacy and safety compared to other treatments – a systematic review and meta-analysis. EFORT Open Reviews. 2024. DOI: 10.1530/EOR-23-0205

[35] Marfan Syndrome: A Clinical Update. Journal of the American Academy of Orthopaedic Surgeons. 2017. DOI: 10.5435/jaaos-d-16-00143

[36] Efficacy of denosumab versus alendronate for aromatase inhibitor-associated osteoporosis in postmenopausal breast cancer patients: a retrospective analysis. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-09280-w

[37] Racial and Ethnic Differences in Osteoporosis. Journal of the American Academy of Orthopaedic Surgeons. 2007. DOI: 10.5435/00124635-200700001-00008

[38] The effect of empagliflozin (sodium–glucose cotransporter-2 inhibitor) on osteoporosis and glycemic parameters in patients with type 2 diabetes: a quasi-experimental study. BMC Musculoskeletal Disorders. 2024. DOI: 10.1186/s12891-024-07900-5

[39] The effects of simvastatin on the bone microstructure and mechanics of ovariectomized mice: a micro-CT and micro-finite element analysis study. BMC Musculoskeletal Disorders. 2024. DOI: 10.1186/s12891-024-07860-w

[40] Comparative analysis of bone turnover markers in bone marrow and peripheral blood: implications for osteoporosis. Journal of Orthopaedic Surgery and Research. 2024. DOI: 10.1186/s13018-024-04634-x

[41] Multidisciplinary consensus on the management of patients with osteopenia and fracture risk in Spain. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-08997-y

[42] Can Bisphosphonate Therapy Reduce Overall Mortality in Patients With Osteoporosis? A Meta-analysis of Randomized Controlled Trials. Clinical Orthopaedics & Related Research. 2024. DOI: 10.1097/corr.0000000000003204

[43] Impact of Teriparatide on Complications and Patient-Reported Outcomes of Patients Undergoing Long Spinal Fusion According to Bone Density. Journal of Bone and Joint Surgery. 2023. DOI: 10.2106/jbjs.23.00272

[44] Chapter 12 Metabolism. 2020.

[45] Pharmacotherapy change patterns after fragility fracture in patients receiving bone-active medication: a fracture liaison service quality improvement cohort study. BMC Musculoskeletal Disorders. 2026. DOI: 10.1186/s12891-026-09548-9

[46] Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications. International Journal of Molecular Sciences. 2021. DOI: 10.3390/ijms22041568

[47] Gout is not associated with the risk of fracture: a meta-analysis. Journal of Orthopaedic Surgery and Research. 2019. DOI: 10.1186/s13018-019-1317-4

[48] Osteometabolism: Metabolic Alterations in Bone Pathologies. Cells. 2022. DOI: 10.3390/cells11233943

[49] The constituents of bone, as determined by analysis, are best illustrated diagrammatically (Fig. 1). The elements of which bone is composed are deposited as a crystalline. 1950.

[50] Associations of blood trace elements with bone mineral density: a population-based study in US adults. Journal of Orthopaedic Surgery and Research. 2023. DOI: 10.1186/s13018-023-04329-9

[51] Treatment of Deformity of the Lower Limb in Adults Who Have Osteogenesis Imperfecta. The Journal of Bone & Joint Surgery*. 1996. DOI: 10.2106/00004623-199602000-00008

[52] Clinical Use of Opportunistic Computed Tomography Screening for Osteoporosis. Journal of Bone and Joint Surgery. 2018. DOI: 10.2106/jbjs.17.01376

[53] The association between body mass index and bone mineral density in older adults: a cross-sectional study of community population in Beijing. BMC Musculoskeletal Disorders. 2024. DOI: 10.1186/s12891-024-07782-7

[54] 18F-fluoride PET/CT as an early predictor of bony fusion after posterior lumbar interbody fusion– a prospective study. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-05814-z

[55] Osteoporosis: Current Modes of Prevention and Treatment. Journal of the American Academy of Orthopaedic Surgeons. 1999. DOI: 10.5435/00124635-199901000-00003

[56] Breaking strength and bone microarchitecture in osteoporosis: a biomechanical approximation based on load tests in 104 human vertebrae from the cervical, thoracic, and lumbar spines of 13 body donors. Journal of Orthopaedic Surgery and Research. 2022. DOI: 10.1186/s13018-022-03105-5

[57] Long-term effect of physical inactivity on osteosarcopenic obesity – a MRI-based investigation from a population-based cohort. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-09266-8

[58] Body composition in males with adolescent idiopathic scoliosis: a case–control study with dual-energy X-ray absorptiometry. BMC Musculoskeletal Disorders. 2016. DOI: 10.1186/s12891-016-0968-0

[59] Opportunistic screening of osteoporosis in lung transplant recipients: diagnostic value of pre-transplant thoracic CT using vertebral Hounsfield units. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-06271-4

[60] Evaluation of Singh Index and Osteoporosis Self-Assessment Tool for Asians as risk assessment tools of hip fracture in patients with type 2 diabetes mellitus. Journal of Orthopaedic Surgery and Research. 2017. DOI: 10.1186/s13018-017-0539-6

[61] Efficacy of traditional Chinese exercise on postmenopausal osteoporosis: a systematic review and meta-analysis. Journal of Orthopaedic Surgery and Research. 2024. DOI: 10.1186/s13018-024-05288-5

[62] Construction of a predictive model for osteoporosis risk in men: using the IOF 1-min osteoporosis test. Journal of Orthopaedic Surgery and Research. 2023. DOI: 10.1186/s13018-023-04266-7

[63] Biomechanical role of osteoporosis affects the incidence of adjacent segment disease after percutaneous transforaminal endoscopic discectomy. Journal of Orthopaedic Surgery and Research. 2019. DOI: 10.1186/s13018-019-1166-1

[64] Metabolic signatures in osteoporotic cancellous bone: a comprehensive dual-platform metabolomic analysis. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-09368-3

[65] The impact of vitamin D status on changes in bone mineral density during treatment with bisphosphonates and after discontinuation following long-term use in post-menopausal osteoporosis. BMC Musculoskeletal Disorders. 2007. DOI: 10.1186/1471-2474-8-3

[66] Role of vertebral fat fraction and R2 based on fat analysis and calculation technique in the quantitative assessment of osteoporosis. BMC Musculoskeletal Disorders*. 2025. DOI: 10.1186/s12891-025-08964-7

[67] Contradictory links between lipid levels and bone health: atherogenic index of plasma and bone microarchitecture. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-05460-5

[68] Osteitis Fibrosa Cystica and pathological fractures—the classic but neglected skeletal manifestation of primary hyperparathyroidism: a case report. BMC Musculoskeletal Disorders. 2021. DOI: 10.1186/s12891-021-04326-1

[69] The role of the combination of bone and fall related risk factors on short-term subsequent fracture risk and mortality. BMC Musculoskeletal Disorders. 2013. DOI: 10.1186/1471-2474-14-121

[70] Whole-body vibration training and bone mineral density in older adults: an updated systematic review and meta-analysis. BMC Musculoskeletal Disorders. 2026. DOI: 10.1186/s12891-026-09504-7

[71] Effects of cyclosporin-a on rat skeletal biomechanical properties. BMC Musculoskeletal Disorders. 2011. DOI: 10.1186/1471-2474-12-240

[72] Effects of continuous subcutaneous insulin infusion on the microstructures, mechanical properties and bone mineral compositions of lumbar spines in type 2 diabetic rats. BMC Musculoskeletal Disorders. 2022. DOI: 10.1186/s12891-022-05452-0

[73] Chapter 12 Physical Examination of the Spine. 2019.

[74] Co-morbid mechanisms of intervertebral disc degeneration and osteoporosis: biomechanical coupling and molecular pathways synergistically driving degenerative lesions. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-06075-6

[75] High-impact exercise in adulthood and vertebral dimensions in midlife - the Northern Finland Birth Cohort 1966 study. BMC Musculoskeletal Disorders. 2017. DOI: 10.1186/s12891-017-1794-8

[76] Chronic low back pain is associated with reduced vertebral bone mineral measures in community-dwelling adults. BMC Musculoskeletal Disorders. 2012. DOI: 10.1186/1471-2474-13-49

[77] 2025 Basic Science Neer Award Winner: The impact of posterior and posterior superior labral injuries and the effect of their treatment on glenohumeral kinematics in the deceleration and follow-through phase of throwing: a biomechanical study. Journal of Shoulder and Elbow Surgery. 2025. DOI: 10.1016/j.jse.2024.12.023

[78] Surgical treatment of thoracolumbar fracture in ankylosing spondylitis: A comparison of percutaneous and open techniques. Journal of Orthopaedic Surgery and Research. 2022. DOI: 10.1186/s13018-022-03378-w

[79] The reduced cortical bone density in vertebral bodies: risk for osteoporotic fractures? Insights from CT analysis. Journal of Orthopaedic Surgery and Research. 2024. DOI: 10.1186/s13018-024-04896-5

[80] Relationship between trabecular bone score, bone mineral density and vertebral fractures in patients with axial spondyloarthritis. BMC Musculoskeletal Disorders. 2023. DOI: 10.1186/s12891-023-06431-9

[81] Osteogenesis Imperfecta: A HISTOPATHOLOGICAL CASE REPORT.. The Journal of Bone and Joint Surgery. American Volume. 1973.

[82] Histology of bone after parathyroid adenectomy. A case report.. The Journal of Bone & Joint Surgery. 1990. DOI: 10.2106/00004623-199072100-00022

[83] Finite element analysis of precise puncture vertebral augmentation in the treatment of different types of osteoporotic vertebral compression fractures. BMC Musculoskeletal Disorders. 2024. DOI: 10.1186/s12891-024-07735-0

[84] A study of the factors associated with cervical spinal disc degeneration, with a focus on bone metabolism and amino acids, in the Japanese population: a cross sectional study. BMC Musculoskeletal Disorders. 2018. DOI: 10.1186/s12891-018-2055-1

[85] Determining the validity and reliability of spinopelvic parameters through comparing standing whole spinal radiographs and upright computed tomography images. BMC Musculoskeletal Disorders. 2021. DOI: 10.1186/s12891-021-04786-5

[86] Three-dimensional morphological analysis of the thoracic pedicle and related radiographic factors in adolescent idiopathic scoliosis. BMC Musculoskeletal Disorders. 2022. DOI: 10.1186/s12891-022-05799-4

Creative Commons BY-NC 4.0

CC Creative Commons licence
BY Attribution — you must credit the source
NC NonCommercial — not for commercial use

Attribution-NonCommercial 4.0 International

Creative Commons Corporation ("Creative Commons") is not a law firm and does not provide legal services or legal advice. Distribution of Creative Commons public licenses does not create a lawyer-client or other relationship. Creative Commons makes its licenses and related information available on an "as-is" basis. Creative Commons gives no warranties regarding its licenses, any material licensed under their terms and conditions, or any related information. Creative Commons disclaims all liability for damages resulting from their use to the fullest extent possible.

Using Creative Commons Public Licenses

Creative Commons public licenses provide a standard set of terms and conditions that creators and other rights holders may use to share original works of authorship and other material subject to copyright and certain other rights specified in the public license below. The following considerations are for informational purposes only, are not exhaustive, and do not form part of our licenses.

Considerations for licensors: Our public licenses are intended for use by those authorized to give the public permission to use material in ways otherwise restricted by copyright and certain other rights. Our licenses are irrevocable. Licensors should read and understand the terms and conditions of the license they choose before applying it. Licensors should also secure all rights necessary before applying our licenses so that the public can reuse the material as expected. Licensors should clearly mark any material not subject to the license. This includes other CC- licensed material, or material used under an exception or limitation to copyright. More considerations for licensors: wiki.creativecommons.org/Considerations_for_licensors

Considerations for the public: By using one of our public licenses, a licensor grants the public permission to use the licensed material under specified terms and conditions. If the licensor's permission is not necessary for any reason--for example, because of any applicable exception or limitation to copyright--then that use is not regulated by the license. Our licenses grant only permissions under copyright and certain other rights that a licensor has authority to grant. Use of the licensed material may still be restricted for other reasons, including because others have copyright or other rights in the material. A licensor may make special requests, such as asking that all changes be marked or described. Although not required by our licenses, you are encouraged to respect those requests where reasonable. More considerations for the public: wiki.creativecommons.org/Considerations_for_licensees

Creative Commons Attribution-NonCommercial 4.0 International Public License

By exercising the Licensed Rights (defined below), You accept and agree to be bound by the terms and conditions of this Creative Commons Attribution-NonCommercial 4.0 International Public License ("Public License"). To the extent this Public License may be interpreted as a contract, You are granted the Licensed Rights in consideration of Your acceptance of these terms and conditions, and the Licensor grants You such rights in consideration of benefits the Licensor receives from making the Licensed Material available under these terms and conditions.

Section 1 -- Definitions.

a. Adapted Material means material subject to Copyright and Similar Rights that is derived from or based upon the Licensed Material and in which the Licensed Material is translated, altered, arranged, transformed, or otherwise modified in a manner requiring permission under the Copyright and Similar Rights held by the Licensor. For purposes of this Public License, where the Licensed Material is a musical work, performance, or sound recording, Adapted Material is always produced where the Licensed Material is synched in timed relation with a moving image.

b. Adapter's License means the license You apply to Your Copyright and Similar Rights in Your contributions to Adapted Material in accordance with the terms and conditions of this Public License.

c. Copyright and Similar Rights means copyright and/or similar rights closely related to copyright including, without limitation, performance, broadcast, sound recording, and Sui Generis Database Rights, without regard to how the rights are labeled or categorized. For purposes of this Public License, the rights specified in Section 2(b)(1)-(2) are not Copyright and Similar Rights.

d. Effective Technological Measures means those measures that, in the absence of proper authority, may not be circumvented under laws fulfilling obligations under Article 11 of the WIPO Copyright Treaty adopted on December 20, 1996, and/or similar international agreements.

e. Exceptions and Limitations means fair use, fair dealing, and/or any other exception or limitation to Copyright and Similar Rights that applies to Your use of the Licensed Material.

f. Licensed Material means the artistic or literary work, database, or other material to which the Licensor applied this Public License.

g. Licensed Rights means the rights granted to You subject to the terms and conditions of this Public License, which are limited to all Copyright and Similar Rights that apply to Your use of the Licensed Material and that the Licensor has authority to license.

h. Licensor means the individual(s) or entity(ies) granting rights under this Public License.

i. NonCommercial means not primarily intended for or directed towards commercial advantage or monetary compensation. For purposes of this Public License, the exchange of the Licensed Material for other material subject to Copyright and Similar Rights by digital file-sharing or similar means is NonCommercial provided there is no payment of monetary compensation in connection with the exchange.

j. Share means to provide material to the public by any means or process that requires permission under the Licensed Rights, such as reproduction, public display, public performance, distribution, dissemination, communication, or importation, and to make material available to the public including in ways that members of the public may access the material from a place and at a time individually chosen by them.

k. Sui Generis Database Rights means rights other than copyright resulting from Directive 96/9/EC of the European Parliament and of the Council of 11 March 1996 on the legal protection of databases, as amended and/or succeeded, as well as other essentially equivalent rights anywhere in the world.

l. You means the individual or entity exercising the Licensed Rights under this Public License. Your has a corresponding meaning.

Section 2 -- Scope.

a. License grant.

1. Subject to the terms and conditions of this Public License, the Licensor hereby grants You a worldwide, royalty-free, non-sublicensable, non-exclusive, irrevocable license to exercise the Licensed Rights in the Licensed Material to:

a. reproduce and Share the Licensed Material, in whole or in part, for NonCommercial purposes only; and

b. produce, reproduce, and Share Adapted Material for NonCommercial purposes only.

2. Exceptions and Limitations. For the avoidance of doubt, where Exceptions and Limitations apply to Your use, this Public License does not apply, and You do not need to comply with its terms and conditions.

3. Term. The term of this Public License is specified in Section 6(a).

4. Media and formats; technical modifications allowed. The Licensor authorizes You to exercise the Licensed Rights in all media and formats whether now known or hereafter created, and to make technical modifications necessary to do so. The Licensor waives and/or agrees not to assert any right or authority to forbid You from making technical modifications necessary to exercise the Licensed Rights, including technical modifications necessary to circumvent Effective Technological Measures. For purposes of this Public License, simply making modifications authorized by this Section 2(a) (4) never produces Adapted Material.

5. Downstream recipients.

a. Offer from the Licensor -- Licensed Material. Every recipient of the Licensed Material automatically receives an offer from the Licensor to exercise the Licensed Rights under the terms and conditions of this Public License.

b. No downstream restrictions. You may not offer or impose any additional or different terms or conditions on, or apply any Effective Technological Measures to, the Licensed Material if doing so restricts exercise of the Licensed Rights by any recipient of the Licensed Material.

6. No endorsement. Nothing in this Public License constitutes or may be construed as permission to assert or imply that You are, or that Your use of the Licensed Material is, connected with, or sponsored, endorsed, or granted official status by, the Licensor or others designated to receive attribution as provided in Section 3(a)(1)(A)(i).

b. Other rights.

1. Moral rights, such as the right of integrity, are not licensed under this Public License, nor are publicity, privacy, and/or other similar personality rights; however, to the extent possible, the Licensor waives and/or agrees not to assert any such rights held by the Licensor to the limited extent necessary to allow You to exercise the Licensed Rights, but not otherwise.

2. Patent and trademark rights are not licensed under this Public License.

3. To the extent possible, the Licensor waives any right to collect royalties from You for the exercise of the Licensed Rights, whether directly or through a collecting society under any voluntary or waivable statutory or compulsory licensing scheme. In all other cases the Licensor expressly reserves any right to collect such royalties, including when the Licensed Material is used other than for NonCommercial purposes.

Section 3 -- License Conditions.

Your exercise of the Licensed Rights is expressly made subject to the following conditions.

a. Attribution.

1. If You Share the Licensed Material (including in modified form), You must:

a. retain the following if it is supplied by the Licensor with the Licensed Material:

i. identification of the creator(s) of the Licensed Material and any others designated to receive attribution, in any reasonable manner requested by the Licensor (including by pseudonym if designated);

ii. a copyright notice;

iii. a notice that refers to this Public License;

iv. a notice that refers to the disclaimer of warranties;

v. a URI or hyperlink to the Licensed Material to the extent reasonably practicable;

b. indicate if You modified the Licensed Material and retain an indication of any previous modifications; and

c. indicate the Licensed Material is licensed under this Public License, and include the text of, or the URI or hyperlink to, this Public License.

2. You may satisfy the conditions in Section 3(a)(1) in any reasonable manner based on the medium, means, and context in which You Share the Licensed Material. For example, it may be reasonable to satisfy the conditions by providing a URI or hyperlink to a resource that includes the required information.

3. If requested by the Licensor, You must remove any of the information required by Section 3(a)(1)(A) to the extent reasonably practicable.

4. If You Share Adapted Material You produce, the Adapter's License You apply must not prevent recipients of the Adapted Material from complying with this Public License.

Section 4 -- Sui Generis Database Rights.

Where the Licensed Rights include Sui Generis Database Rights that apply to Your use of the Licensed Material:

a. for the avoidance of doubt, Section 2(a)(1) grants You the right to extract, reuse, reproduce, and Share all or a substantial portion of the contents of the database for NonCommercial purposes only;

b. if You include all or a substantial portion of the database contents in a database in which You have Sui Generis Database Rights, then the database in which You have Sui Generis Database Rights (but not its individual contents) is Adapted Material; and

c. You must comply with the conditions in Section 3(a) if You Share all or a substantial portion of the contents of the database.

For the avoidance of doubt, this Section 4 supplements and does not replace Your obligations under this Public License where the Licensed Rights include other Copyright and Similar Rights.

Section 5 -- Disclaimer of Warranties and Limitation of Liability.

a. UNLESS OTHERWISE SEPARATELY UNDERTAKEN BY THE LICENSOR, TO THE EXTENT POSSIBLE, THE LICENSOR OFFERS THE LICENSED MATERIAL AS-IS AND AS-AVAILABLE, AND MAKES NO REPRESENTATIONS OR WARRANTIES OF ANY KIND CONCERNING THE LICENSED MATERIAL, WHETHER EXPRESS, IMPLIED, STATUTORY, OR OTHER. THIS INCLUDES, WITHOUT LIMITATION, WARRANTIES OF TITLE, MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, NON-INFRINGEMENT, ABSENCE OF LATENT OR OTHER DEFECTS, ACCURACY, OR THE PRESENCE OR ABSENCE OF ERRORS, WHETHER OR NOT KNOWN OR DISCOVERABLE. WHERE DISCLAIMERS OF WARRANTIES ARE NOT ALLOWED IN FULL OR IN PART, THIS DISCLAIMER MAY NOT APPLY TO YOU.

b. TO THE EXTENT POSSIBLE, IN NO EVENT WILL THE LICENSOR BE LIABLE TO YOU ON ANY LEGAL THEORY (INCLUDING, WITHOUT LIMITATION, NEGLIGENCE) OR OTHERWISE FOR ANY DIRECT, SPECIAL, INDIRECT, INCIDENTAL, CONSEQUENTIAL, PUNITIVE, EXEMPLARY, OR OTHER LOSSES, COSTS, EXPENSES, OR DAMAGES ARISING OUT OF THIS PUBLIC LICENSE OR USE OF THE LICENSED MATERIAL, EVEN IF THE LICENSOR HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH LOSSES, COSTS, EXPENSES, OR DAMAGES. WHERE A LIMITATION OF LIABILITY IS NOT ALLOWED IN FULL OR IN PART, THIS LIMITATION MAY NOT APPLY TO YOU.

c. The disclaimer of warranties and limitation of liability provided above shall be interpreted in a manner that, to the extent possible, most closely approximates an absolute disclaimer and waiver of all liability.

Section 6 -- Term and Termination.

a. This Public License applies for the term of the Copyright and Similar Rights licensed here. However, if You fail to comply with this Public License, then Your rights under this Public License terminate automatically.

b. Where Your right to use the Licensed Material has terminated under Section 6(a), it reinstates:

1. automatically as of the date the violation is cured, provided it is cured within 30 days of Your discovery of the violation; or

2. upon express reinstatement by the Licensor.

For the avoidance of doubt, this Section 6(b) does not affect any right the Licensor may have to seek remedies for Your violations of this Public License.

c. For the avoidance of doubt, the Licensor may also offer the Licensed Material under separate terms or conditions or stop distributing the Licensed Material at any time; however, doing so will not terminate this Public License.

d. Sections 1, 5, 6, 7, and 8 survive termination of this Public License.

Section 7 -- Other Terms and Conditions.

a. The Licensor shall not be bound by any additional or different terms or conditions communicated by You unless expressly agreed.

b. Any arrangements, understandings, or agreements regarding the Licensed Material not stated herein are separate from and independent of the terms and conditions of this Public License.

Section 8 -- Interpretation.

a. For the avoidance of doubt, this Public License does not, and shall not be interpreted to, reduce, limit, restrict, or impose conditions on any use of the Licensed Material that could lawfully be made without permission under this Public License.

b. To the extent possible, if any provision of this Public License is deemed unenforceable, it shall be automatically reformed to the minimum extent necessary to make it enforceable. If the provision cannot be reformed, it shall be severed from this Public License without affecting the enforceability of the remaining terms and conditions.

c. No term or condition of this Public License will be waived and no failure to comply consented to unless expressly agreed to by the Licensor.

d. Nothing in this Public License constitutes or may be interpreted as a limitation upon, or waiver of, any privileges and immunities that apply to the Licensor or You, including from the legal processes of any jurisdiction or authority.

Creative Commons is not a party to its public licenses. Notwithstanding, Creative Commons may elect to apply one of its public licenses to material it publishes and in those instances will be considered the “Licensor.” The text of the Creative Commons public licenses is dedicated to the public domain under the CC0 Public Domain Dedication. Except for the limited purpose of indicating that material is shared under a Creative Commons public license or as otherwise permitted by the Creative Commons policies published at creativecommons.org/policies, Creative Commons does not authorize the use of the trademark "Creative Commons" or any other trademark or logo of Creative Commons without its prior written consent including, without limitation, in connection with any unauthorized modifications to any of its public licenses or any other arrangements, understandings, or agreements concerning use of licensed material. For the avoidance of doubt, this paragraph does not form part of the public licenses.

Creative Commons may be contacted at creativecommons.org.