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Purpose of Review: We review the literature about patients 50 years and older with a recent clinical fracture for the presence of skeletal and extra-skeletal risks, their perspectives of imminent subsequent fracture, falls, mortality, and other risks, and on the role of the fracture liaison service (FLS) for timely secondary fracture prevention. Recent Findings: Patients with a recent clinical fracture present with heterogeneous patterns of bone-, fall-, and comorbidity-related risks. Short-term perspectives include bone loss, increased risk of fractures, falls, and mortality, and a decrease in physical performance and quality of life. Combined evaluation of bone, fall risk, and the presence of associated comorbidities contributes to treatment strategies. Summary: Since fractures are related to interactions of bone-, fall-, and comorbidity-related risks, there is no one-single-discipline-fits-all approach but a need for a multidisciplinary approach at the FLS to consider all phenotypes for evaluation and treatment in an individual patient. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a lifestyle-related disease that develops in middle-aged and older adults, often due to smoking habits, and has been noted to cause bone fragility. COPD is a risk factor for osteoporosis and fragility fracture, and a high prevalence of osteoporosis and incidence of vertebral fractures have been shown in patients with COPD. Findings of lung tissue analysis in patients with COPD are primarily emphysema with a loss of alveolar septal walls, and the severity of pulmonary emphysema is negatively correlated with thoracic spine bone mineral density (BMD). On the other hand, epidemiological studies on COPD and fracture risk have reported a BMD-independent increase in fracture risk; however, verification in animal models and human bone biopsy samples has been slow, and the essential pathogenesis has not been elucidated. The detailed pathological/molecular mechanisms of musculoskeletal complications in patients with COPD are unknown, and basic research is needed to elucidate the mechanisms. This paper discusses the impacts of COPD on bone strength, focusing on findings in animal models in terms of bone microstructure, bone metabolic dynamics, and material properties. [ABSTRACT FROM AUTHOR]

Myasthenia gravis is an autoimmune disease in which autoantibodies affect the neuromuscular junction, leading to muscle loss. Steroids are the primary immunosuppressive treatment for this condition. Since steroids affect the immune system and are effective in most subtypes of myasthenia gravis, they are often used for long-term maintenance treatment. This increases the probability of steroidassociated side effects such as decreases in bone mineral density and increased risk of fractures. The authors successfully treated an 18-year-old female who had been using steroids for a long time after being diagnosed with myasthenia gravis using teriparatide for osteoporotic multi-segment thoracolumbar compression fractures that occurred without trauma with satisfactory outcomes. Since there have been no reports of osteoporotic multi-segmental thoracolumbar compression fractures and treatment in juvenile myasthenia gravis patients caused by long-term steroid use, we report this case along with a review of the literature. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate the effects of romosozumab on bone mineral density (BMD) and bone metabolism. Methods: In this retrospective case series, romosozumab was administered to 5 premenopausal female patients with osteoporosis and anorexia nervosa with fragility fractures. BMD and bone turnover marker changes were investigated at 6 months and 1 year after administering romosozumab. Results: BMD increased and high-turnover bone metabolism decreased 6 months and 1 year after administering romosozumab. Conclusions: Romosozumab is useful for treating osteoporosis in patients with anorexia nervosa.

A 47-year-old postmenopausal woman with osteoporosis was treated with denosumab, which was discontinued due to side effects. She was therefore transitioned to a yearly intravenous infusion of zoledronic acid. An increase in bone turnover markers together with bone loss at the lumbar spine was observed before the second infusion, suggesting an overshooting of bone resorption due to denosumab discontinuation. On physical examination, the patient was restless and reported having lost about 10 kg since the last visit. A solitary left inferior thyroid nodule was noted on neck palpation. Circulating thyroid hormone levels were elevated, with suppressed thyroid-stimulating hormone. A thyroid scan showed increased uptake in the left inferior nodule with suppression of the remainder of the thyroid gland. A diagnosis of hyperthyroidism due to toxic adenoma was made. The patient was treated with radioactive iodine ablation, with consequent complete normalization of thyroid function. She continued yearly treatment with zoledronic acid. She remained clinically well with no further fractures. Bone turnover markers were appropriately suppressed and bone mineral density increased in the spine and hip. This case illustrates how the overshooting phenomenon following denosumab discontinuation may be compounded by the development of secondary conditions, which can result in suboptimal response to antiresorptive osteoporosis medications. [ABSTRACT FROM AUTHOR]

Introduction: Hormonal therapy (HT) blocks the hormone-mediated growth signal dramatically reducing estrogenic levels with aromatase inhibitors (AIs) becoming a crucial component of the treatment mainstay in patients with early breast cancer (BC). Postmenopausal BC patients receiving HT present with a significant risk of secondary osteoporosis with AIs further reducing estrogen levels and ultimately leading to an accelerated rate of bone resorption and thus decreased bone mineral density (BMD). This was an observational retrospective clinical study that consecutively enrolled early BC patients with osteopenia to compare the impact of alendronate versus denosumab on secondary osteoporosis prevention and pain control. Methods: We identified two groups of patients treated with denosumab 60 mg by subcutaneous injection once every six months or alendronate 70 mg orally once a week. All the patients underwent a baseline physiatric evaluation (T0) and underwent a follow-up visit after 18 months (T1) together with femoral and vertebral Dual-Energy X-ray Absorptiometry (DEXA) exam evaluating T-Score marks. From September 2015 to December 2019 a total of 50 early (stage I-III) BC patients were considered eligible and consecutively enrolled in our study if they met pre-specified inclusion criteria. Results: In the entire observed population, the addition of treatment with alendronate or denosumab led to a significant T-score improvement at the lumbar spine level (-1.92 vs -1.52, p=0.03), with a comparable contribution from alendronate (-1.60 vs -1.45, p=0.07) and denosumab (-2.26 vs -1.58, p=0.07). Regarding the femoral region, neither alendronate (-0.98 vs -1.07, p=0.23) nor denosumab (-1.39 vs -1.34, p=0.81) were able to produce any statistically relevant effect. However, concerning pain control, BMAs had a significant impact on reducing NRS scoresin the general population (T1 3.94 vs. baseline 4.32, p=0.007), with a likelyspecific contribution from alendronate (T1 3.52 vs. baseline 3.88, p=0.004) compared to denosumab (T1 4.36 vs baseline 4.76, p=0.12), without any differences in analgesic therapy assumption over time (p=0.93). Discussion: Both alendronate and denosumab significantly contributed to preventing secondary osteoporosis in early BC patients with low BMD undergoing AIs, mostly at the lumbar spine level. Moreover, alendronate seemed to significantly impact pain control in such patients further supporting alendronate as a costeffective option in this frail setting, although BMAs particularities should be carefully considered on an individual basis according to specific clinical contexts. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease in adults that is associated with significant joint issues and systemic inflammation. One of the signs of bone damage in RA is osteoporosis (OP). Leptin is an inflammatory protein that has been reported to be related to RA. The potential relationships among leptin, disease activity, and OP in Chinese patients with RA are not well known. Methods: In total, 245 patients with RA and 120 healthy controls were included in this study. Detailed data on the clinical characteristics and laboratory features were collected. Information about physical activity and functional status was recorded using specific questionnaires. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). The MECALL castor-50-hf model X-ray scanner was used for the two-hand (including wrist) photographs. Results: Serum leptin levels differed significantly between the RA group and healthy control subjects (1.27/3.29 vs. 0.17/0.24, Z=13.29, P<0.001). The positive rate of leptin protein in RA patients was 86.35%, which was higher than that in controls (19.55%) (χ2=28.51, P<0.001). Pearson's correlation test showed that morning stiffness, disease duration, joint swelling, joint tenderness, swollen joint count (SJC), tender joint count (TJC), health assessment questionnaire (HAQ) score, and Sharp-van der Heijde method (Sharp) score were positively correlated with the level of serum leptin (r=0.212, r=0.312, r=0.322, r=0.501, r=0.291, r=0.334, P<0.05). There was a clear increasing trend in the level of serum leptin according to the different disease activity scores and in the 28 joint activity (DAS28) groups (F=13.936, P<0.001). Elevated leptin was a risk factor for increased disease activity and OP according to logistic regression analysis. The median leptin level differed significantly between the normal bone mass group, osteopenia group, and OP group (P<0.001). An increased serum leptin level was a risk factor for RA-induced osteoporosis according to logistic regression analysis (P<0.001). Conclusion: These results suggest that the level of serum leptin is associated with disease activity and secondary OP among Chinese patients with RA. Key Points • Serum leptin levels in RA patients are higher than those in normal control group. • Leptin was associated with disease activity. • Leptin was associated with the occurrence of systemic osteoporosis and affects bone erosion in RA patients. [ABSTRACT FROM AUTHOR]

Objectives: Graves' disease (GD) is the most common cause of thyrotoxicosis. There are many studies that have evaluated bone mineral density (BMD) in Graves’ disease. However, the strength of a bone also depends on its microarchitecture which can be assessed by various techniques. Trabecular bone score (TBS) is a new method for assessing bone microarchitecture that is non-invasive and easily performed. Methods: The present study was a cross-sectional study that involved 50 patients with active GD and 50 healthy controls. Both groups were subjected to an assessment of biochemical parameters followed by measurement of BMD and TBS on the same dual energy X-ray absorptiometry (DXA) machine. Results: The mean age of patients with active GD (N = 50) was 31.9 ± 10.9 years while that of controls was 31.2 ± 4.9 years (P = 0.640). The female: male ratio was the same for both groups (F = 31, M = 19). The mean lumbar spine BMD, femoral neck BMD, total hip BMD, and distal radius BMD were significantly reduced in GD when compared to that in controls. The mean absolute lumbar spine TBS in GD was 1.263 ± 0.101 while that in controls was 1.368 ± 0.073 (P

Summary: Identifying secondary causes among osteoporotic patients is crucial. However, there is no simple tool for screening secondary osteoporosis. A predictive model for screening secondary osteoporosis was constructed using simple clinical and biochemical parameters. This predictive model may provide clinicians with guidance to perform further investigations for specific causes of osteoporosis. Purpose: Establishing whether a fragility fracture is secondary to a specific cause of osteoporosis is crucial for treatment outcomes. Therefore, this study aimed to develop a simple screening tool for secondary osteoporosis in the elderly initially presented with fragility fractures. Methods: A retrospective cohort study including 456 patients with fragility hip and vertebral fractures that occurred between January 2017 and July 2022 was conducted. Demographic, clinical, biochemical, and final diagnostic data were retrieved. Potential predictors for secondary osteoporosis were determined by multivariable logistic regression analysis, and a predictive model for secondary osteoporosis was subsequently developed using identified potential predictors. Results: This study included 343 females and 113 males with a mean age of 76.9 ± 11.0 years. One hundred and twenty-one patients (26.5%) were diagnosed with secondary osteoporosis. Vitamin D deficiency (71.9%) was the most common cause of secondary osteoporosis, followed by glucocorticoid-induced osteoporosis (23.9%) and primary hyperparathyroidism (9.9%). The potential predictors for secondary osteoporosis included in the predictive model were age, body mass index (BMI), corrected calcium, phosphate, thyroid stimulating hormone, and a 10-year probability of hip fractures calculated by BMI-based FRAX®. With a cut-off level of 0.22, the proposed predictive model has an AuROC of 0.75 (95% CI 0.69 to 0.81) with a sensitivity of 77%, a specificity of 66%, and an accuracy of 68.9%. Conclusion: A predictive model for screening secondary osteoporosis was constructed using simple clinical and biochemical parameters. This newly developed predictive model may provide clinicians with guidance to perform further advanced investigations for secondary causes of osteoporosis. [ABSTRACT FROM AUTHOR]

Patients with systemic mastocytosis (SM) are at high risk of bone deterioration. However, the evaluation of bone microarchitecture in this disease remains unclear. We aimed to assess bone microarchitecture in patients with SM. This was a cross-sectional study of 21 adult patients with SM conducted in a quaternary referral hospital in Sao Paulo, Brazil. A healthy, age-, weight-, and sex-matched cohort of 63 participants was used to provide reference values for bone microarchitecture, assessed by high resolution peripheral quantitative computed tomography (HR-pQCT). Total volumetric bone mineral density (vBMD), cortical vBMD, and cortical thickness at the radius were significantly lower in the control group compared with the SM group (all P < 0.001). Patients with aggressive SM had significantly lower trabecular number (Tb.N) (P = 0.035) and estimated failure load (F.load) (P = 0.032) at the tibia compared with those with indolent SM. Handgrip strength was significantly higher in patients who had more Tb.N at the radius (ρ, 0.46; P = 0.036) and tibia (ρ, 0.49; P = 0.002), and lower who had more trabecular separation at the radius (ρ, −0.46; P = 0.035) and tibia (ρ, −0.52; P = 0.016). Strong and positive associations between F.load (ρ, 0.75; P < 0.001) and stiffness (ρ, 0.70; P < 0.001) at the radius, and between F.load at the tibia (ρ, 0.45; P = 0.038) were observed with handgrip strength. In this cross-sectional study, aggressive SM was more susceptible to bone deterioration compared with indolent SM. In addition, the findings demonstrated that handgrip strength was associated with bone microarchitecture and bone strength. [ABSTRACT FROM AUTHOR]

IntroductionDiabetic bone disease is characterized by an increased fracture risk which may be partly attributed to deficits in cortical bone quality such as higher cortical porosity. However, the temporal evolution of bone microarchitecture, strength, and particularly of cortical porosity in diabetic bone disease is still unknown. Here, we aimed to prospectively characterize the 5-year changes in bone microarchitecture, strength, and cortical porosity in type 2 diabetic (T2D) postmenopausal women with (DMFx) and without history of fragility fractures (DM) and to compare those to nondiabetic fracture free controls (Co) using high resolution peripheral quantitative computed tomography (HR-pQCT).MethodsThirty-two women underwent baseline HR-pQCT scanning of the ultradistal tibia and radius and a FU-scan 5 years later. Bone microarchitectural parameters, including cortical porosity, and bone strength estimates via µFEA were calculated for each timepoint and annualized. Linear regression models (adjusted for race and change in BMI) were used to compare the annualized percent changes in microarchitectural parameters between groups.ResultsAt baseline at the tibia, DMFx subjects exhibited the highest porosity of the three groups (66.3% greater Ct.Po, 71.9% higher Ct.Po.Volume than DM subjects, p < 0.022). Longitudinally, porosity increased significantly over time in all three groups and at similar annual rates, while DMFx exhibited the greatest annual decreases in bone strength indices (compared to DM 4.7× and 6.7× greater decreases in failure load [F] and stiffness [K], p < 0.025; compared to Co 14.1× and 22.2× greater decreases in F and K, p < 0.020).ConclusionOur data suggest that despite different baseline levels in cortical porosity, T2D women with and without fractures experienced long-term porosity increases at a rate similar to non-diabetics. However, the annual loss in bone strength was greatest in T2D women with a history of a fragility fractures. This suggests a potentially non-linear course of cortical porosity development in T2D bone disease: major porosity may develop early in the course of disease, followed by a smaller steady annual increase in porosity which in turn can still have a detrimental effect on bone strength-depending on the amount of early cortical pre-damage.

IntroductionHormonal therapy (HT) blocks the hormone-mediated growth signal dramatically reducing estrogenic levels with aromatase inhibitors (AIs) becoming a crucial component of the treatment mainstay in patients with early breast cancer (BC). Postmenopausal BC patients receiving HT present with a significant risk of secondary osteoporosis with AIs further reducing estrogen levels and ultimately leading to an accelerated rate of bone resorption and thus decreased bone mineral density (BMD). This was an observational retrospective clinical study that consecutively enrolled early BC patients with osteopenia to compare the impact of alendronate versus denosumab on secondary osteoporosis prevention and pain control.MethodsWe identified two groups of patients treated with denosumab 60 mg by subcutaneous injection once every six months or alendronate 70 mg orally once a week. All the patients underwent a baseline physiatric evaluation (T0) and underwent a follow-up visit after 18 months (T1) together with femoral and vertebral Dual-Energy X-ray Absorptiometry (DEXA) exam evaluating T-Score marks. From September 2015 to December 2019 a total of 50 early (stage I-III) BC patients were considered eligible and consecutively enrolled in our study if they met pre-specified inclusion criteria. ResultsIn the entire observed population, the addition of treatment with alendronate or denosumab led to a significant T-score improvement at the lumbar spine level (-1.92 vs -1.52, p=0.03), with a comparable contribution from alendronate (-1.60 vs -1.45, p=0.07) and denosumab (-2.26 vs -1.58, p=0.07). Regarding the femoral region, neither alendronate (-0.98 vs -1.07, p=0.23) nor denosumab (-1.39 vs -1.34, p=0.81) were able to produce any statistically relevant effect. However, concerning pain control, BMAs had a significant impact on reducing NRS scoresin the general population (T1 3.94 vs. baseline 4.32, p=0.007), with a likelyspecific contribution from alendronate (T1 3.52 vs. baseline 3.88, p=0.004) compared to denosumab (T1 4.36 vs baseline 4.76, p=0.12), without any differences in analgesic therapy assumption over time (p=0.93).DiscussionBoth alendronate and denosumab significantly contributed to preventing secondary osteoporosis in early BC patients with low BMD undergoing AIs, mostly at the lumbar spine level. Moreover, alendronate seemed to significantly impact pain control in such patients further supporting alendronate as a cost-effective option in this frail setting, although BMAs particularities should be carefully considered on an individual basis according to specific clinical contexts.

The trabecular bone score (TBS) can be determined in addition to the Dual Energy X-ray Absorptiometry (DXA) for bone mineral density (BMD) measurement to diagnose, evaluate, and stratify bone loss and decide on appropriate treatment in patients at risk. Especially in patients with secondary osteoporosis, TBS detects restricted bone quality. To investigate the influence of an additional evaluation of TBS on patients' treatment strategy decisions, we enrolled 292 patients, with a high proportion of patients with secondary osteoporosis, from one outpatient unit over one year. Patients eligible for BMD measurement had the option to opt-in for TBS measurement. We analyzed demographic data, leading diagnoses, bone metabolism parameters, and results of BMD and TBS measurements. More than 90% of patients consented to TBS measurement. TBS measurement influenced the decision in approximately 40% of patients with a treatment indication for anti-osteoporotic drugs. We demonstrate that depending on the underlying disease/risk spectrum, 21–25.5% of patients had an unremarkable BMD measurement with poor bone quality shown in the TBS measurement. In patients with secondary osteoporosis, the use of TBS supplementary to DXA seems useful to better assess fracture risk and, thus, to initiate therapy for osteoporosis in these patients in time. [ABSTRACT FROM AUTHOR]

Haemophilia A (HA) and haemophilia B (HB) are X-linked inherited bleeding disorders caused by the absence or deficiency of coagulation factors VIII (FVIII) and IX (FIX), respectively. Recent advances in the development of effective treatments for haemophilia have led to a significant increase in life expectancy. As a result, the incidence of some comorbidities, including fragility fractures, has increased in people with haemophilia (PWH). The aim of our research was to perform a review of the literature investigating the pathogenesis and multidisciplinary management of fractures in PWH. The PubMed, Scopus and Cochrane Library databases were searched to identify original research articles, meta-analyses, and scientific reviews on fragility fractures in PWH. The mechanism underlying bone loss in PWH is multifactorial and includes recurrent joint bleeding, reduced physical activity with consequent reduction in mechanical load, nutritional deficiencies (particularly vitamin D), and FVIII and FIX deficiency. Pharmacological treatment of fractures in PWH includes antiresorptive, anabolic and dual action drugs. When conservative management is not possible, surgery is the preferred option, particularly in severe arthropathy, and rehabilitation is a key component in restoring function and maintaining mobility. Appropriate multidisciplinary fracture management and an adapted and tailored rehabilitation pathway are essential to improve the quality of life of PWH and prevent long-term complications. Further clinical trials are needed to improve the management of fractures in PWH. [ABSTRACT FROM AUTHOR]

ABSTRACT Trabecular bone score (TBS) is an indirect and noninvasive measure of bone quality. A low TBS indicates degraded bone microarchitecture, predicts osteoporotic fracture, and is partially independent of clinical risk factors and bone mineral density (BMD). There is substantial evidence supporting the use of TBS to assess vertebral, hip, and major osteoporotic fracture risk in postmenopausal women, as well as to assess hip and major osteoporotic fracture risk in men aged > 50 years. TBS complements BMD information and can be used to adjust the FRAX (Fracture Risk Assessment) score to improve risk stratification. While TBS should not be used to monitor antiresorptive therapy, it may be potentially useful for monitoring anabolic therapy. There is also a growing body of evidence indicating that TBS is particularly useful as an adjunct to BMD for fracture risk assessment in conditions associated with increased fracture risk, such as type-2 diabetes, chronic corticosteroid excess, and other conditions wherein BMD readings are often misleading. The interference of abdominal soft tissue thickness (STT) on TBS should also be considered when interpreting these findings because image noise can impact TBS evaluation. A new TBS software version based on an algorithm that accounts for STT rather than BMI seems to correct this technical limitation and is under development. In this paper, we review the current state of TBS, its technical aspects, and its evolving role in the assessment and management of several clinical conditions.

Aim: We aimed to improve bone health management of children with cerebral palsy (CP) by reviewing studies investigating bisphosphonate therapy in children with CP and other types of secondary osteoporosis. Methods: We included trials on bisphosphonate treatment reporting any direct bone measurement or fracture outcome. All studies of patients with CP were included. We also included all controlled trials of children with secondary bone fragility as well as observational studies with ≥20 participants or at least 3 years of follow‐up. Studies were assessed according to PRISMA guidelines using the RoB2‐tool and the Newcastle‐Ottawa Scale. Results: We reviewed 1104 studies and found 37 eligible. Some studies were sufficiently homogeneous to include in a meta‐analysis, and we found a 1‐year effect on lumbar spine bone mineral density (BMD) Z‐score of +0.65 after oral and + 1.21 after intravenous bisphosphonates in children with secondary osteoporosis. Further, data on adverse events and post‐treatment follow‐up were reviewed. Limitations were heterogeneity and small size of the included studies. Conclusion: Meta‐analysis consistently showed significant BMD increases with bisphosphonates in children with secondary osteoporosis. Direct evidence of the effect of bisphosphonates on reducing fractures is lacking. We found no reports of long‐term adverse events yet longer studies are needed. [ABSTRACT FROM AUTHOR]

By definition, children constitute a vulnerable population, especially when they are chronically ill and/or disabled. A characteristic of chronically ill and disabled children is that they also suffer from indirect effects of their disease, such as immobilization, chronic inflammation, reduced time outdoors in the sun, osteotoxic effects of disease-targeted therapy (like glucocorticoids), and poor nutrition. All these factors may lead to bone fragility due to secondary osteoporosis, a co-morbidity that may be overlooked in the context of serious underlying diseases. The ultimate goal of osteoporosis diagnosis and monitoring in this setting is the early identification, prevention, and treatment of low-trauma long bone and vertebral fractures; indeed, vertebral fractures are a frequently under-diagnosed manifestation of overt bone fragility in this context. Efforts to prevent first-ever fractures are also meritorious, including encouragement of weight-bearing activities, optimization of nutritional status, including calcium and vitamin D supplementation, and the diagnosis and treatment of delayed growth and puberty; however, these conservative measures may be insufficient in those at high risk. Numerous natural history studies have shown that vertebral fractures are more common than non-vertebral (i.e., long bone) fractures in at-risk children. Not surprisingly, the cornerstone of secondary osteoporosis monitoring is lateral spine imaging for the early detection of vertebral collapse. Although dual-energy x-ray absorptiometry (DXA) is the gold standard to measure bone mineral density, digital X-ray radiogrammetry may be used as a surrogate measure of bone strength if dual-energy x-ray absorptiometry is not available. In the event that preventive measures fail, treatment with bisphosphonates may be appropriate. Typically, treatment with intravenous bisphosphonates is reserved for children with overt bone fragility and limited potential for spontaneous recovery. However, there is increasing attention to very high-risk children, such as boys with Duchenne muscular dystrophy, who may benefit from bisphosphonate therapy prior to first-ever fractures (given their high fracture frequency and essentially absent potential for spontaneous recovery). This article provides a contemporary overview of the definition and diagnosis of osteoporosis in children with chronic illness, along with the approach to monitoring those at risk and the evidence for currently recommended intervention strategies. [ABSTRACT FROM AUTHOR]

Introduction Established scores estimate 10-year fracture risk in osteoporosis to assist with treatment recommendations. This study compared the risk probabilities of major osteoporotic and hip fractures calculated by the FRAX tool with those of the DVO score, established in German-speaking countries. Material and Methods This seven-year retrospective study analyzed data of 125 male patients (mean age: 59.2±10.7 years) evaluated for osteoporosis. For the DVO score, the therapy threshold of>30% for vertebral and hip fractures suggested by DVO guidelines was implemented. We calculated fracture risks based on FRAX scores with aBMD and applied a common therapy threshold of≥3% for hip fracture and subsequently determined the "DVO-equivalent risk level" for FRAX-based assessment that would identify as many male patients as identified by the DVO score. Results Based on DVO score, 60.0% of patients had a 10-year risk of hip and vertebral fractures>30%. The recommendations for individuals based on FRAX scores for hip fracture with aBMD with risk≥3% overlapped with those based on DVO score in 36% of patients. Patients identified for treatment only by DVO score presented a higher percentage of spine fractures (65 vs. 41%). The thresholds for this "DVO-equivalent risk level" for 'FRAX with aBMD' was estimated to be≥6.7% for major osteoporotic fracture and≥2.1% for hip fracture. This study demonstrates that the DVO score was more sensitive than the FRAX score for patients with prevalent spinal fractures. We suggest considering the appropriate score and therapy threshold carefully in the daily care of male patients. [ABSTRACT FROM AUTHOR]

Objective: Children with chronic diseases are at a risk of inadequate bone mineralization due to the effects of the primary disease and/or treatment. The aim of this study was to evaluate the clinical characteristics and treatment responses of patients with secondary osteoporosis. Methods: Forty-four patients with chronic diseases who had bone mineral density (BMD) Z-score of ≤-2.0 on the dual-energy X-ray absorptiometry (DXA) were included. Results: Age at diagnosis of osteoporosis was 9.2±4.9 years (1.4-17.7 years). Chronic disease groups were defined as gastrointestinal (29.5%), neurological (22.7%), hematologic (18.2%), inborn errors in metabolism (11.4%), rheumatologic (9.1%), and renal (9.1%). The rate of receiving steroid treatment was 63.6%. DXA Z-score was -2.8±0.9. The fracture frequency in the long bones was 20.5%. Bisphosphonate (BP) treatment was given in 34.1% (n = 15) of the patients. BP was the most commonly used in neurological diseases (50%). A significant difference was found between the initial and final DXA Z-scores in BP patients (-3.3±1.0 and -2.4±0.9; p=0.004). Conclusion: In our study, a heterogeneous group of chronic systemic diseases was evaluated, and BP treatment provided a significant improvement in BMD. Further prospective studies are still required in which clinical and radiological improvements are evaluated in large groups of patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the clinical factors associated with bone mineral density (BMD) among children and adolescents with osteoporosis secondary to treatment for underlying clinical conditions. Methods: We retrospectively reviewed the medical records of patients aged 10–18 years and evaluated them for lumbar spine BMD (LSBMD) after treatment for underlying diseases, including hemato-oncologic, rheumatologic system, and inflammatory bowel diseases. LSBMD measured by dual-energy x-ray absorptiometry (DXA) performed from March 2019 to March 2021 was evaluated. We analyzed 117 patients who underwent initial DXA after treatment for underlying diseases. Results: Subjects in this study had multiple underlying diseases: hemato-oncologic (78.6%), rheumatologic (11.1%), and inflammatory bowel diseases (10.3%). There was no significant association between the z-score and bone metabolic markers (P>0.05). However, higher cumulative glucocorticoid (GC) dose significantly reduced LSBMD z-score (P=0.029). Moreover, the association between cumulative dose of GC and initial z-score of LSBMD was significant in logarithmic regression analysis (P=0.003, R² =0.149). GC accumulation was a significant risk factor for vertebral fracture when the initial BMD was evaluated after treatment (P=0.043). Bone metabolic markers did not significantly influence the risk of vertebral fracture. Conclusion: Initial bone mass density of the lumbar spine evaluated after long-term GC use for underlying diseases is a predictor of further vertebral fractures. [ABSTRACT FROM AUTHOR]

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Various bone and joint pathology is quite common among companion animals, a significant risk factor for which is considered to be a violation of bone metabolism. The aim of the work is to determine radiological and pathochemical criteria in the dynamics of osteoporosis process in the model of rabbits. The experimental (n = 18) and control (n = 9) groups of animals were formed. Experimental osteoporosis in rabbits of the experimental group was caused by the administration of 0.4% solution of dexamethasone (4 mg / ml) (KRKA, Slovenia) for the 21st day at a dose of 1.2 mg / kg body weight 1 time / day. Control animals were injected with saline. Blood samples for biochemical studies were taken before the induction of osteoporosis and on the 7th, 14th, 21st day. Serum levels of total calcium (Ca) and phosphorus, activity of total alkaline phosphatase and its bone isoenzyme, tartrate-resistant acid phosphatase were determined. Measurements were performed with a spectrophotometer Stat Fax 4500. X-ray examinations were performed on an X-ray machine RUM-20 before the induction of osteoporosis and on the 7th, 14th, 21st day of the study. On the 14th day of the study, some areas of the spongy substance of the proximal femur have the appearance of a large-loop pattern due to the resorption of individual bone beams. There is also an expansion of the bone marrow canal due to bone resorption, thinning and emphasizing the edges of the cortical layer. On the 21st day, changes characteristic of osteoporosis were observed - low intensity of X-ray contrast shadow of bone, significant thinning of bone structure. Radiographically established changes in bone tissue correlate with biochemical parameters of rabbit blood. On the 21st day of osteoporosis induction in experimental animals, the level of total Ca decreased 2.1 times (p

Purpose This study aimed to investigate the clinical factors associated with bone mineral density (BMD) among children and adolescents with osteoporosis secondary to treatment for underlying clinical conditions. Methods We retrospectively reviewed the medical records of patients aged 10–18 years and evaluated them for lumbar spine BMD (LSBMD) after treatment for underlying diseases, including hemato-oncologic, rheumatologic system, and inflammatory bowel diseases. LSBMD measured by dual-energy x-ray absorptiometry (DXA) performed from March 2019 to March 2021 was evaluated. We analyzed 117 patients who underwent initial DXA after treatment for underlying diseases. Results Subjects in this study had multiple underlying diseases: hemato-oncologic (78.6%), rheumatologic (11.1%), and inflammatory bowel diseases (10.3%). There was no significant association between the z-score and bone metabolic markers (P>0.05). However, higher cumulative glucocorticoid (GC) dose significantly reduced LSBMD z-score (P=0.029). Moreover, the association between cumulative dose of GC and initial z-score of LSBMD was significant in logarithmic regression analysis (P=0.003, R2=0.149). GC accumulation was a significant risk factor for vertebral fracture when the initial BMD was evaluated after treatment (P=0.043). Bone metabolic markers did not significantly influence the risk of vertebral fracture. Conclusions Initial bone mass density of the lumbar spine evaluated after long-term GC use for underlying diseases is a predictor of further vertebral fractures.

Hyperthyroidism causes secondary osteoporosis through favoring bone resorption over bone formation, leading to bone loss with elevated bone fragility. Osteocytes that reside within lacunae inside the mineralized bone matrix orchestrate the process of bone remodeling and can themselves actively resorb bone upon certain stimuli. Nevertheless, the interaction between thyroid hormones and osteocytes and the impact of hyperthyroidism on osteocyte cell function are still unknown. In a preliminary study, we analyzed bones from male C57BL/6 mice with drug‐induced hyperthyroidism, which led to mild osteocytic osteolysis with 1.14‐fold larger osteocyte lacunae and by 108.33% higher tartrate‐resistant acid phosphatase (TRAP) activity in osteocytes of hyperthyroid mice compared to euthyroid mice. To test whether hyperthyroidism‐induced bone changes are reversible, we rendered male mice hyperthyroid by adding levothyroxine into their drinking water for 4 weeks, followed by a weaning period of 4 weeks with access to normal drinking water. Hyperthyroid mice displayed cortical and trabecular bone loss due to high bone turnover, which recovered with weaning. Although canalicular number and osteocyte lacunar area were similar in euthyroid, hyperthyroid and weaned mice, the number of terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling (TUNEL)‐positive osteocytes was 100% lower in the weaning group compared to euthyroid mice and the osteocytic TRAP activity was eightfold higher in hyperthyroid animals. The latter, along with a 3.75% lower average mineralization around the osteocyte lacunae in trabecular bone, suggests osteocytic osteolysis activity that, however, did not result in significantly enlarged osteocyte lacunae. In conclusion, we show a recovery of bone microarchitecture and turnover after reversal of hyperthyroidism to a euthyroid state. In contrast, osteocytic osteolysis was initiated in hyperthyroidism, but its effects were not reversed after 4 weeks of weaning. Due to the vast number of osteocytes in bone, we speculate that even minor individual cell functions might contribute to altered bone quality and mineral homeostasis in the setting of hyperthyroidism‐induced bone disease. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Objective: To summarize the clinical features and bone complications in a patient from a large family with X-linked congenital adrenocortical hypoplasia (AHC) and evaluate the efficacy of different treatment regimens on the prognosis of secondary osteoporosis caused by AHC at a 5-year follow-up. Methods: A large family with AHC was recruited, and the causative gene mutation was identified by Sanger sequencing in the proband. Clinical features as well as radiological examinations and laboratory indices of osteoporosis secondary to AHC were analyzed in this study. Meanwhile, the proband was treated with classical antiresorptive drugs (bisphosphonates) for 2 years and switched to a vitamin K2 analogue for another 3 years, during which the efficacy of the drugs was evaluated. Results: The proband was identified as carrying a homozygous insertion mutation (p. Thr193GlyfsX13) in the NR0B1 (nuclear receptor subfamily 0, group B, member 1) gene, resulting in a premature stop codon due to a frameshift mutation. During treatment and follow-up, the proband did not respond well to bisphosphonate and developed atypical femoral fractures. Vitamin K2 improved clinical symptoms. In terms of bone mineral density (BMD), there is no evidence of any effect of vitamin K2 on the neck of femur, though some minor effects on spinal BMD cannot be excluded. Conclusions: Secondary osteoporosis induced by AHC deserves clinical attention. Unlike in primary osteoporosis, the curative effect of bisphosphonates was unsatisfactory and was more likely to cause atypical femoral fractures in long-term treatment. It is suggested that bone anabolic drugs may be better alternatives. [ABSTRACT FROM AUTHOR]

Secondary osteoporosis has been associated with cancer patients undertaking Doxorubicin (DOX) chemotherapy. However, the molecular mechanisms behind DOX-induced bone loss have not been elucidated. Molecules that can protect against the adverse effects of DOX are still a challenge in chemotherapeutic treatments. We investigated the effect and mechanism of DOX in osteoclast differentiation and used the Sirt 1 activator resveratrol (RES) to counteract DOX-induced effects. RAW 264.7 cells were differentiated into osteoclasts under cotreatment with DOX and RES, alone or combined. RES treatment inhibited DOX-induced osteoclast differentiation, reduced the expression of osteoclast fusion marker Oc-stamp and osteoclast differentiation markers Rank, Trap, Ctsk and Nfatc1. Conversely, RES induced the upregulation of antioxidant genes Sod 1 and Nrf 2 while DOX significantly reduced the FoxM1 expression, resulting in oxidative stress. Treatment with the antioxidant MitoTEMPO did not influence DOX-induced osteoclast differentiation. DOX-induced osteoclastogenesis was studied using the cathepsin-K zebrafish reporter line (Tg[ctsk:DsRed]). DOX significantly increased ctsk signal, while RES cotreatment resulted in a significant reduction in ctsk positive cells. RES significantly rescued DOX-induced mucositis in this model. Additionally, DOX-exposed zebrafish displayed altered locomotor behavior and locomotory patterns, while RES significantly reversed these effects. Our research shows that RES prevents DOX-induced osteoclast fusion and activation in vitro and in vivo and reduces DOX-induced mucositis, while improving locomotion parameters. [ABSTRACT FROM AUTHOR]

Osteoporosis is characterized by an abnormal bone structure with low bone mass and degradation of microarchitecture. Oxidative stress induces imbalances in osteoblast and osteoclast activity, leading to bone degradation, a primary cause of secondary osteoporosis. Doxorubicin (DOX) is a widely used chemotherapy drug for treating cancer, known to induce secondary osteoporosis. The mechanism underlying DOX-induced bone loss is still not fully understood, but one of the relevant mechanisms is through a massive accumulation of reactive oxygen and nitrogen species (i.e., ROS and NOS) leading to oxidative stress. We investigated the effects of antioxidants Resveratrol and MitoTEMPO on DOX-induced bone impairment using the zebrafish model. DOX was shown to increase mortality, promote skeletal deformities, induce alterations on intestinal villi, impair growth and mineralization and significantly downregulate osteoblast differentiation markers osteocalcin 2 and osterix/sp7. Lipid peroxidation was significantly increased in DOX-supplemented groups as compared to control and antioxidants, suggesting ROS formation as one of the key factors for DOX-induced bone loss. Furthermore, DOX affected mineral contents, suggesting an altered mineral metabolism. However, upon supplementation with antioxidants, DOX-induced effects on mineral content were rescued. Our data show that supplementation with antioxidants effectively improves the overall growth and mineralization in zebrafish and counteracts DOX-induced bone anomalies. [ABSTRACT FROM AUTHOR]

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• High-risk women under the age of 65 years should be screened for osteoporosis. • All women with a history of fragility fractures, regardless of age, should be screened and potentially treated for osteoporosis. • Younger women with osteoporosis are more likely to have secondary causes, and clinicians should make screening for osteoporosis a priority for these high-risk women. For women under age 65, varying recommendations and the need to apply clinical risk calculators can lead to underscreening for osteoporosis. The resulting undertreatment may lead to a risk of osteoporotic fractures with significant morbidity and impact on functional status. Factors that must be considered when deciding to screen a woman under age 65 include a history of fragility fractures, race, family history, body mass index, smoking, high alcohol use, and secondary causes of osteoporosis. Secondary causes of osteoporosis are much more common in younger women. These include common conditions such as glucocorticoid use, hyperthyroidism, hypogonadism, chronic kidney disease, diabetes, anticonvulsant use, rheumatoid arthritis, malabsorption, and a history of anorexia nervosa. The reasons why these conditions confer an increased risk of osteoporosis are discussed. Recommendations are provided for the clinician to be aware of when screening women under age 65 for osteoporosis and initiating treatment when indicated. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: Rheumatoid arthritis (RA) is a significant issue, particularly in bone health problems, because it can prolong diseases like secondary osteoporosis. Subsequently, the anchor of drug therapy for RA is methotrexate (MTX), which also has the potential to reduce the risk of secondary osteoporosis. Objective: This study aims to examine the effect of MTX on calcium levels, an important parameter for monitoring bone health and the risk of secondary osteoporosis in patients with RA. Methods: A retrospective study was carried out by collecting data from the medical records of patients, which included demographic and patient characteristics, treatment data (drug and dosage), duration of treatment, and calcium levels. All patients were diagnosed with RA and fell within the age range of 18 to 59 years. Additionally, the effectiveness of MTX therapy was compared with other treatments, categorizing patient data accordingly. Statistical analyses, such as χ2 and ordinal regression, using IBM-SPSS Statistics version 25 (IBM-SPSS Inc, Armonk, New York) were used to establish associations between MTX treatment and calcium levels, reporting odds ratio and 95% CI values. Results: The data consisted of 123 patients with RA, comprising 99 who had a history of MTX use for more than 6 months and 24 who either did not use MTX or used it for

ObjectivesA fracture risk assessment tool (FRAX) using clinical risk factors (CRFs) alone underestimates fracture risk in HIV-infected men. Our objective was to determine whether accuracy of FRAX would be improved by considering HIV as a cause of secondary osteoporosis, and further improved with addition of dual-energy X-ray absorptiometry parameters in HIV-infected women.DesignSubgroup analysis of Women's Interagency HIV Study.MethodsWe included 1148 women (900 HIV-infected and 248 uninfected) over age 40 with data to approximate FRAX CRFs and 10-year observational data for incident fragility fractures; 181 (20%) HIV-infected women had dual-energy X-ray absorptiometry data. Accuracy of FRAX was evaluated by the observed/estimated ratios of fracture in four models: CRFs alone; CRFs with HIV included as a cause of secondary osteoporosis; CRFs and femoral neck bone mineral density (FN BMD); and CRFs, FN BMD and trabecular bone score.ResultsFRAX using CRFs were less accurate in HIV-infected than uninfected women for major osteoporotic (observed/estimated ratio: 5.05 vs. 3.26, P

Bilateral adrenal tumors (BAT) represent a vast domain of endocrinology and connected medical and surgical fields. Our purpose is to introduce several key points in relationship with long time management on a 56-year old female case who is currently admitted for reassessment of a left adrenal tumor with potential autonomous cortisol secretion. She is also known with pituitary incidentaloma since 2014, cerebral meningioma which was partially removed in 2015, uncontrolled diabetes mellitus under metformin and insulin therapy since 2017, and high blood pressure since 2021. Her medical history includes right adrenalectomy for Cushing syndrome in 2014. At that moment, she was first admitted for BAT, a tumor of 2 centimeters (cm) on the left gland according to computed tomography, respective of 3.5 cm maximum diameter on the right adrenal. The hormonal panel confirmed adrenal Cushing syndrome. After 6 months of non-interventional follow-up, the right tumor increased to 4 cm, also associating small areas of necrosis, thus a decision of unilateral laparoscopic adrenalectomy was done with good clinical post-operatory outcome. She did not develop adrenal insufficiency at any point in time, moreover, a low-normal ACTH (Adrenocorticotrop Hormone) with intermittent elevation of morning plasma cortisol levels after Dexamethasone suppression test showed a possible autonomous cortisol secretion of the left adrenal tumor during a 7-year follow-up. In 2014, the female patient received the confirmation of an adrenocortical adenoma which was consistent with cortisol over-secretion. Particular gene contributions are attributed to protein kinase A (PKA) defects (or B) that usually induce bilateral adrenocortical hyperplasia; however, they are not routinely tested in daily endocrine practice, neither had we performed it. Interestingly, the patient was detected with a cerebral meningioma after years of intermittent, mild headache. The diagnostic was established during initial endocrine evaluations. The headache was not associated with uncontrolled high blood pressure, as first expected due to excessive cortisol amount. Recently, it was identified that mutations of ARMC5 (armadillo repeat containing 5) gene are responsible for macronodular adrenal hyperplasia, but also meningioma. They may be also responsible for severe diabetes mellitus as seen here. The key points of following a patient with bilateral adrenal tumors include the timing of uni/bilateral adrenalectomy, the multidisciplinary management of associated complications, as well as the need of understanding the genetic rational behind it.

Microgravity-induced bone loss is a major concern for space travelers. Ground-based microgravity simulators are crucial to study the effect of microgravity exposure on biological systems and to address the limitations posed by restricted access to real space. In this work, for the first time, we adopt a multidisciplinary approach to characterize the morphological, biochemical, and molecular changes underlying the response of human bone marrow stromal cells to long-term simulated microgravity exposure during osteogenic differentiation. Our results show that osteogenic differentiation is reduced while energy metabolism is promoted. We found novel proteins were dysregulated under simulated microgravity, including CSC1-like protein, involved in the mechanotransduction of pressure signals, and PTPN11, SLC44A1 and MME which are involved in osteoblast differentiation pathways and which may become the focus of future translational projects. The investigation of cell proteome highlighted how simulated microgravity affects a relatively low number of proteins compared to time and/or osteogenic factors and has allowed us to reconstruct a hypothetical pipeline for cell response to simulated microgravity. Further investigation focused on the application of nanomaterials may help to increase understanding of how to treat or minimize the effects of microgravity. [ABSTRACT FROM AUTHOR]

Purpose: The diagnostic criteria for osteoporosis are based on the bone mineral density (BMD) level in the lumbar spine and femur bone. Patients with osteoporotic fractures were diagnosed with osteoporosis. While systemic BMD and mandibular cortical bone morphology are correlated, this has not been studied in patients with a history of osteoporotic fractures. Therefore, purpose of this study was researching the mandibular cortical bone morphology in patients with osteoporotic fractures. Methods: The subjects were 55 female and 20 male patients with osteoporotic fractures. Patients were divided into 30 primary osteoporosis patients and 45 secondary osteoporosis patients according to the medical history. Patients underwent BMD and panoramic radiography examinations during orthopedic treatment for fractures. A dual-energy X-ray absorptiometry system was used to measure BMD. Mandibular cortex index (MCI) and mandibular cortex width (MCW) were evaluated using machine-learning measurement software. Results: In the analysis of MCI, the ratio of class 2 and 3 was 73% of both primary osteoporosis and secondary osteoporosis. The average MCW was 2.19 mm for primary osteoporosis and 2.30 mm for secondary osteoporosis. The sensitivity values by MCI and MCW were 73% and 76% for both primary and secondary osteoporosis, which were similar detection powers. In addition, the false-negative rates by MCI and MCW were 27% and 24%. Conclusion: We suggested that MCI and MCW are indicators of osteoporotic conditions in patients with primary and secondary osteoporosis. Our results show that MCI and MCW are non-inferior to the sensitivity values for lumbar BMD in patients with osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Early recognition of osteoporosis in children and adolescents is important in order to establish an appropriate diagnosis of the underlying condition and to initiate treatment if necessary. In this review, we present the diagnostic work-up, and its pitfalls, of pediatric patients suspected of osteoporosis including a careful collection of the medical and personal history, a complete physical examination, biochemical data, molecular genetics, and imaging techniques. The most recent and relevant literature has been reviewed to offer a broad overview on the topic. Genetic and acquired pediatric bone disorders are relatively common and cause substantial morbidity. In recent years, there has been significant progress in the understanding of the genetic and molecular mechanistic basis of bone fragility and in the identification of acquired causes of osteoporosis in children. Specifically, drugs that can negatively impact bone health (e.g. steroids) and immobilization related to acute and chronic diseases (e.g. Duchenne muscular dystrophy) represent major risk factors for the development of secondary osteoporosis and therefore an indication to screen for bone mineral density and vertebral fractures. Long-term studies in children chronically treated with steroids have resulted in the development of systematic approaches to diagnose and manage pediatric osteoporosis. Conclusions: Osteoporosis in children requires consultation with and/or referral to a pediatric bone specialist. This is particularly relevant since children possess the unique ability for spontaneous and medication-assisted recovery, including reshaping of vertebral fractures. As such, pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children. What is Known: • Both genetic and acquired pediatric disorders can compromise bone health and predispose to fractures early in life. • The identification of children at risk of osteoporosis is essential to make a timely diagnosis and start the treatment, if necessary. What is New: • Pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children and children at risk of osteoporosis. • We offer an extensive but concise overview about the risk factors for osteoporosis and the diagnostic work-up (and its pitfalls) of pediatric patients suspected of osteoporosis. [ABSTRACT FROM AUTHOR]

Intestinal microecology is composed of normal intestinal flora and the environment they live in. It is the most important and complex microecosystem of human body and plays an important role in the normal growth and development of human body. In recent years, many studies have discussed the correlation between intestinal flora and osteoporosis. This article attempts to discuss the possible mechanism of alcohol-induced osteoporosis from the effect of alcohol on intestinal microecology. It is believed that long-term and large alcohol intake changes the composition of flora and intestinal environment, destroys the stability of intestinal microecology, increases bacteroidetes, and decreases firmicutes (especially lactobacillus). In addition to the influence of alcohol induced oxidative stress, alcohol intake directly or indirectly destroys the balance of bone metabolism, eventually leading to the occurrence of alcohol-induced osteoporosis. [ABSTRACT FROM AUTHOR]

Haemophilia A (HA) and haemophilia B (HB) are X-linked inherited bleeding disorders caused by the absence or deficiency of coagulation factors VIII (FVIII) and IX (FIX), respectively. Recent advances in the development of effective treatments for haemophilia have led to a significant increase in life expectancy. As a result, the incidence of some comorbidities, including fragility fractures, has increased in people with haemophilia (PWH). The aim of our research was to perform a review of the literature investigating the pathogenesis and multidisciplinary management of fractures in PWH. The PubMed, Scopus and Cochrane Library databases were searched to identify original research articles, meta-analyses, and scientific reviews on fragility fractures in PWH. The mechanism underlying bone loss in PWH is multifactorial and includes recurrent joint bleeding, reduced physical activity with consequent reduction in mechanical load, nutritional deficiencies (particularly vitamin D), and FVIII and FIX deficiency. Pharmacological treatment of fractures in PWH includes antiresorptive, anabolic and dual action drugs. When conservative management is not possible, surgery is the preferred option, particularly in severe arthropathy, and rehabilitation is a key component in restoring function and maintaining mobility. Appropriate multidisciplinary fracture management and an adapted and tailored rehabilitation pathway are essential to improve the quality of life of PWH and prevent long-term complications. Further clinical trials are needed to improve the management of fractures in PWH.

By definition, children constitute a vulnerable population, especially when they are chronically ill and/or disabled. A characteristic of chronically ill and disabled children is that they also suffer from indirect effects of their disease, such as immobilization, chronic inflammation, reduced time outdoors in the sun, osteotoxic effects of disease-targeted therapy (like glucocorticoids), and poor nutrition. All these factors may lead to bone fragility due to secondary osteoporosis, a co-morbidity that may be overlooked in the context of serious underlying diseases. The ultimate goal of osteoporosis diagnosis and monitoring in this setting is the early identification, prevention, and treatment of low-trauma long bone and vertebral fractures; indeed, vertebral fractures are a frequently under-diagnosed manifestation of overt bone fragility in this context. Efforts to prevent first-ever fractures are also meritorious, including encouragement of weight-bearing activities, optimization of nutritional status, including calcium and vitamin D supplementation, and the diagnosis and treatment of delayed growth and puberty; however, these conservative measures may be insufficient in those at high risk. Numerous natural history studies have shown that vertebral fractures are more common than non-vertebral (i.e., long bone) fractures in at-risk children. Not surprisingly, the cornerstone of secondary osteoporosis monitoring is lateral spine imaging for the early detection of vertebral collapse. Although dual-energy x-ray absorptiometry (DXA) is the gold standard to measure bone mineral density, digital X-ray radiogrammetry may be used as a surrogate measure of bone strength if dual-energy x-ray absorptiometry is not available. In the event that preventive measures fail, treatment with bisphosphonates may be appropriate. Typically, treatment with intravenous bisphosphonates is reserved for children with overt bone fragility and limited potential for spontaneous recovery. However, there is increasing attention to very high-risk children, such as boys with Duchenne muscular dystrophy, who may benefit from bisphosphonate therapy prior to first-ever fractures (given their high fracture frequency and essentially absent potential for spontaneous recovery). This article provides a contemporary overview of the definition and diagnosis of osteoporosis in children with chronic illness, along with the approach to monitoring those at risk and the evidence for currently recommended intervention strategies.

Bone is an extremely dynamic and adaptive tissue, whose metabolism and homeostasis is influenced by many different hormonal, mechanical, nutritional, immunological and pharmacological stimuli. Genetic factors significantly affect bone health, through their influence on bone cells function, cartilage quality, calcium and vitamin D homeostasis, sex hormone metabolism and pubertal timing. In addition, optimal nutrition and physical activity contribute to bone mass acquisition in the growing age. All these factors influence the attainment of peak bone mass, a critical determinant of bone health and fracture risk in adulthood. Secondary osteoporosis is an important issue of clinical care in children with acute and chronic diseases. Systemic autoimmune disorders, like juvenile idiopathic arthritis, can affect the skeletal system, causing reduced bone mineral density and high risk of fragility fractures during childhood. In these patients, multiple factors contribute to reduce bone strength, including systemic inflammation with elevated cytokines, reduced physical activity, malabsorption and nutritional deficiency, inadequate daily calcium and vitamin D intake, use of glucocorticoids, poor growth and pubertal delay. In juvenile arthritis, osteoporosis is more prominent at the femoral neck and radius compared to the lumbar spine. Nevertheless, vertebral fractures are an important, often asymptomatic manifestation, especially in glucocorticoid-treated patients. A standardized diagnostic approach to the musculoskeletal system, including prophylaxis, therapy and follow up, is therefore mandatory in at risk children. Here we discuss the molecular mechanisms involved in skeletal homeostasis and the influence of inflammation and chronic disease on bone metabolism. [ABSTRACT FROM AUTHOR]

Objective: Dual x-ray absorptiometry (DXA) is gold standard of bone densitometry, but quantitative ultrasound (QUS) of bone is less expensive and portable. This study was designed to assess its usefulness in secondary osteoporosis diagnosis. Materials and Methods: There were 200 secondary osteoporosis cases (rheumatoid arthritis, hemodialysis, kidney transplant patients, and levothyroxine users) and of those, their phalanx QUS results were compared with normal controls. Also, the QUS and DXA results were compared to find any correlation of these methods for diagnosing osteoporosis. Results: There was not significantly different results compared with normal controls, except for those of hemodialysis patients (P =.00). Also, the comparison of QUS with DXA results showed no significant correlation except in hemodialysis patients, in both spinal and femoral regions (P =.023 and.21, respectively), as well as the levothyroxine group's spinal region (P =.005). Conclusion: These results suggest that QUS of phalanx may be useful in screening secondary osteoporosis but for establishment of diagnosis, DXA measurements are still needed. [ABSTRACT FROM AUTHOR]