Association between socioeconomic deprivation and bone health status in the UK biobank cohort participants.

The effect of deprivation on total bone health status has not been well defined. We examined the relationship between socioeconomic deprivation and poor bone health and falls and we found a significant association. The finding could be beneficial for current public health strategies to minimise disparities in bone health. PURPOSE: Socioeconomic deprivation is associated with many illnesses including increased fracture incidence in older people. However, the effect of deprivation on total bone health status has not been well defined. To examine the relationship between socioeconomic deprivation and poor bone health and falls, we conducted a cross-sectional study using baseline measures from the United Kingdom (UK) Biobank cohort comprising 502,682 participants aged 40-69 years at recruitment during 2006-2010. METHOD: We examined four outcomes: 1) low bone mineral density/osteopenia, 2) fall in last year, 3) fracture in the last five years, and 4) fracture from a simple fall in the last five years. To measure socioeconomic deprivation, we used the Townsend index of the participant's residential postcode. RESULTS: At baseline, 29% of participants had low bone density (T-score of heel < -1 standard deviation), 20% reported a fall in the previous year, and 10% reported a fracture in the previous five years. Among participants experiencing a fracture, 60% reported the cause as a simple fall. In the multivariable logistic regression model after controlling for other covariates, the odds of a fall, fracture in the last five years, fractures from simple fall, and osteopenia were respectively 1.46 times (95% confidence interval [CI] 1.42-1.49), 1.26 times (95% CI 1.22-1.30), 1.31 times (95% CI 1.26-1.36) and 1.16 times (95% CI 1.13-1.19) higher for the most deprived compared with the least deprived quantile. CONCLUSION: Socioeconomic deprivation was significantly associated with poor bone health and falls. This research could be beneficial to minimise social disparities in bone health.

Reference-Class Problems Are Real: Health-Adjusted Reference Classes and Low Bone Mineral Density.

Elselijn Kingma argues that Christopher Boorse's biostatistical theory (the BST) does not show how the reference classes it uses are objective and naturalistic. Recently, philosophers of medicine have attempted to rebut Kingma's concerns. I argue that these rebuttals are theoretically unconvincing, and that there are clear examples of physicians adjusting their reference classes according to their prior knowledge of health and disease. I focus on the use of age-adjusted reference classes to diagnose low bone mineral density in children. In addition to using the BST's age, sex, and species, physicians also choose to use other factors to define reference classes, such as pubertal status, bone age, body size, and muscle mass. I show that physicians calibrate the reference classes they use according to their prior knowledge of health and disease. Reference classes are also chosen for pragmatic reasons, such as to predict fragility fractures.

Association of a Polygenic Risk Score With Osteoporosis in People Living With HIV: The Swiss HIV Cohort Study.

BACKGROUND: Bone mineral density (BMD) loss may be accelerated in people with HIV (PLWH). It is unknown whether a polygenic risk score (PRS) is associated with low BMD in PLWH. METHODS: Swiss HIV Cohort Study participants of self-reported European descent underwent ≥2 per-protocol dual x-ray absorptiometry (DXA) measurements ≥2 years apart (2011-2020). Univariable and multivariable odds ratios (ORs) for DXA-defined osteoporosis were based on traditional and HIV-related risk factors and a genome-wide PRS built from 9413 single-nucleotide polymorphisms associated with low BMD in the general population. Controls were free from osteoporosis/osteopenia on all DXA measurements. RESULTS: We included 438 participants: 149 with osteoporosis and 289 controls (median age, 53 years; 82% male, 95% with suppressed HIV RNA). Participants with unfavorable osteoporosis PRS (top vs bottom quintile) had univariable and multivariable-adjusted osteoporosis ORs of 4.76 (95% CI, 2.34-9.67) and 4.13 (1.86-9.18), respectively. For comparison, hepatitis C seropositivity, 5-year tenofovir disoproxil fumarate exposure, and parent history of hip fracture yielded univariable osteoporosis ORs of 2.26 (1.37-3.74), 1.84 (1.40-2.43), and 1.54 (0.82-2.9). CONCLUSIONS: In PLWH in Switzerland, osteoporosis was independently associated with a BMD-associated PRS after adjustment for established risk factors, including exposure to tenofovir disoproxil fumarate.

Low bone mineral density, a neglected condition in North Africa and Middle East: estimates from the Global Burden of Disease Study, 1990-2019.

Due to the high prevalence of low bone mineral density in North Africa and Middle East region, estimating its attributable burden would help to a better understanding of this neglected condition for policymakers and health researchers. This study presented the number of attributable deaths has doubled from 1990 to 2019. PURPOSE: This study provides the latest estimates of the burden of low bone mineral density (BMD) from 1990 to 2019 in North Africa and Middle East (NAME) region. METHODS: The data were extracted from the global burden of disease (GBD) 2019 study to estimate epidemiological indices such as deaths, disability-adjusted life years (DALYs), and summary exposure value (SEV). SEV is a measure of the exposure of the population to a risk factor that considers the amount of exposure by the level of risk. RESULTS: Our findings showed that in 1990-2019, the number of deaths and DALYs attributable to low BMD had almost doubled in the region and caused 20,371 (95% uncertainty intervals: 14,848-24,374) deaths and 805,959 (630,238-959,581) DALYs in 2019. However, DALYs and death rates showed a decreasing trend after age standardization. Saudi Arabia had the highest, and Lebanon had the lowest age-standardized DALYs rates in 2019, with rates of 434.2 (329.6-534.3) and 90.3 (70.6-112.1) per 100,000, respectively. The highest burden attributable to low BMD was in the 90-94 and over 95 age groups. Also, there was a decreasing trend in age-standardized SEV to low BMD for both sexes. CONCLUSION: Despite the decreasing trend of age-standardized burden indices, considerable amounts of deaths and DALYs were attributable to low BMD, especially in the elderly population, in the region in 2019. As the positive effects of proper interventions will be detectable in the long term, robust strategies and comprehensive stable policies are the ultimate solutions to achieving desired goals.

Differences in the global exposure, mortality and disability of low bone mineral density between men and women: the underestimated burden in men.

Talking about osteoporosis, we tend to focus on post-menopause women who are at increased risk due to estrogen depletion, while less attention has been paid to the disease in men. Currently, there is a lack of understanding about the difference of osteoporosis incidence and burden by sex. In this study, we used data from the Global Burden of Disease Study 2019 (GBD 2019) to compare the difference in the prevalence and burden of low bone mineral density (LBMD) between men and women, by location, year, age and socio-demographic index. We found the prevalence of LBMD was higher in women than in men. However, the age standardized mortality rate was greatly higher in men than in women. Using disability-adjusted life year (DALY) to measure the burden, we also observed higher age standardized DALY rate in men. Using sociodemographic index (SDI) as the measure of social development level, we found that higher mortality and DALY rates were mainly seen in middle and high SDI countries. Falls were the leading cause for of deaths and disabilities in both men and women with LBMD, followed by transport injuries. Fall-related mortality was higher in women, while transport injuries caused more deaths and disabilities in men. Conclusively, more attention should be paid to osteoporosis in men, and related policies, clinical practices, and guidelines are in need to reduce the burden of LBMD and osteoporosis in men.

Prevalence of delayed puberty and low bone density in patients with epidermolysis bullosa: Insight from a large single center's experience.

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare genetic skin conditions that result in skin fragility. EB can be quite severe with chronic inflammation and malnutrition impairing growth and pubertal development. These factors have potential consequences for skeletal health. We aimed to determine the prevalence of delayed puberty and low bone mineral density (BMD) for age in children and young adults with EB. METHODS: Electronic medical records (EMR) of patients with confirmed EB <30 years of age at time of initial encounter at Cincinnati Children's Hospital Medical Center between January 1, 2010 and September 30, 2020 were reviewed. Natural language processing software was used to categorize pubertal status of patients with EB as early, normal or delayed. BMD was measured by dual energy x-ray absorptiometry and categorized as low if height adjusted Z-score was <-2.0 using age, sex and race specific reference ranges. RESULTS: 29% of individuals with EB had low BMD with most cases occurring prior to 10 years of age. Of patients who reached adolescence, 23% failed to develop any signs of puberty in the normal range (before age 13 in females or 14 in males) and BMD Z-scores further declined in these individuals. CONCLUSION: Delayed puberty is an under-recognized comorbidity of individuals with EB, especially in those with recessive dystrophic EB, and can have a significant impact on BMD.

Clinical and Genetic Characteristics of Calvarial Doughnut Lesions with Bone Fragility in Three Families with a Reccurent SGMS2 Gene Variant.

Calvarial doughnut lesions (CDL) with bone fragility with or without spondylometaphyseal dysplasia (MIM: #126550) is a rare autosomal dominant skeletal disorder characterized by low bone mineral density, spinal and peripheral fractures, and specific sclerotic lesions of the cranial bones. In the current classification of skeletal disorders, the disease is included in the group of bone fragility disorders along with osteogenesis imperfecta. The disease is caused by pathogenic variants in the SGMS2 gene, the protein product of which is sphingomyelin synthase 2, which primarily contributes to sphingomyelin (SM) synthesis-the main lipid component of the plasma membrane essential for bone mineralization. To date, 15 patients from eight families with CDL with bone fragility have been described in the literature, and a recurrent variant c.148C>T (p.Arg50Ter) in the SGMS2 gene has been identified, which was found in patients from six families. We diagnosed the disease in 11 more patients from three unrelated families, caused by the same heterozygous nonsense variant c.148C>T (p.Arg50Ter) in the SGMS2 gene. Our results show wide interfamilial and intrafamilial phenotypic variability in patients with a detected recurrent variant in the SGMS2 gene, the presence of which must be taken into consideration in the diagnosis of the disease. The primary analysis of this variant will contribute to optimal molecular genetic diagnostics, which can reduce diagnostic costs and time.

Using a Polygenic Score to Predict the Risk of Developing Primary Osteoporosis.

Osteoporosis (OP) is a multifactorial bone disease belonging to the metabolic osteopathies group. Using the polygenic score (PGS) approach, we combined the effects of bone mineral density (BMD) DNA loci, affecting osteoporosis pathogenesis, based on GEFOS/GENOMOS consortium GWAS meta-analysis. We developed models to predict the risk of low fractures in women from the Volga-Ural region of Russia with efficacy of 74% (AUC = 0.740; OR (95% CI) = 2.9 (2.353-3.536)), as well as the formation of low BMD with efficacy of 79% (AUC = 0.790; OR (95% CI) = 3.94 (2.993-5.337)). In addition, we propose a model that predicts fracture risk and low BMD in a comorbid condition with 85% accuracy (AUC = 0.850; OR (95% CI) = 6.6 (4.411-10.608)) in postmenopausal women.

Does Supplemental Estrogen Improve Bone-Related Symptoms of Female Athlete Triad in Female Athletes? A Critically Appraised Topic.

Clinical Scenario: Due to the Female Athlete Triad (Triad) being a 3-pronged syndrome, treatments can vary depending on the symptoms that clinicians focus on. With reproductive and bone health compromised, assessment and recovery methods include monitoring menstrual regularity and dual-energy X-ray absorptiometry scans. Low levels of estrogen have demonstrated negative effects on bone mineral density (BMD). Clinical Question: Does supplemental estrogen improve BMD in athletes with Female Athlete Triad symptoms? Summary of Key Findings: Supplemental estrogen does improve BMD with estrogen patches demonstrating increased improvement compared with oral contraceptive pills. Clinical Bottom Line: Restoration of regular menstruation, improvement of BMD, and ensuring optimal energy levels is the best approach for treating Triad symptoms. Transdermal patches are a new treatment option that address both menstrual function and BMD but still require further research. Strength of Recommendation: Available studies demonstrated a level 2 evidence for supplemental estrogen (oral contraceptive pills and estrogen patches) providing improvements for bone health related to the Triad.

Value of quantitative ultrasound and bioelectrical impedance analysis in detecting low bone mineral density in hemodialysis.

INTRODUCTION: Patients on maintenance hemodialysis (MHD) are highly predisposed to low bone mineral density (BMD). This study aims to assess the value of quantitative ultrasound (QUS), bioelectrical impedance analysis (BIA), and their combination in detecting high-risk patients for low BMD in MHD. METHODS: Patients' BMD of the total hip, femoral neck, and lumbar spine were measured using dual-energy X-ray absorptiometry (DXA). Bone mineral content (BMC) was assessed using BIA. Calcaneal BMD was measured using QUS. Patients with a T-score of ≤-2.5 were recorded as 'low BMD.' RESULTS: Overall, 93 subjects (62.37% female; mean age, 60.8 ± 16.2 years) were included in this cross-sectional study; approximately 36.56% met the 'low BMD' criteria. QUS-T score predicted low BMD with an area under the curve (AUC) value of 0.738, sensitivity of 70.59%, and specificity of 76.27%. The AUC for low BMD diagnosis using the BMC index (BMCI) measured through BIA was 0.679 (sensitivity, 91.18%; specificity, 38.98%). On the other hand, the combination of QUS-T score and BMCI yielded a higher AUC value of 0.762 with an improved specificity of 88.14%. Compared with the QUS and BIA alone, the net reclassification improvement (NRI) of the combination model increased by 47.16% (p = 0.022) and 78.36% (p < 0.0001), respectively. Integrated discrimination improvement (IDI) increased by 5.25% (p = 0.043) and 9.99% (p = 0.003), respectively. QUS-T score and BMCI were related to BMD independently assessed by DXA. CONCLUSION: The combination of QUS and BIA is effective in screening for low BMD among MHD patients.

Alendronate Improves Bone Mineral Density in Children and Adolescents Perinatally Infected With Human Immunodeficiency Virus With Low Bone Mineral Density for Age.

BACKGROUND: Children and adolescents with perinatal human immunodeficiency virus (HIV) infection and with low bone mineral density (BMD) may be at higher risk of osteoporosis and fractures in later life than their uninfected peers. Bisphosphonate therapy has been shown to reduce fractures in adults with osteoporosis, but has not been formally studied in youths living with HIV. METHODS: Fifty-two children and adolescents (aged 11-24 years) perinatally infected with HIV with low lumbar spine (LS) BMD (Z score < -1.5) were randomized to receive once-weekly alendronate or placebo in a double-blind cross-over study designed to assess the safety and efficacy of 48 and 96 weeks of alendronate in the United States and Brazil. All participants received daily calcium carbonate and vitamin D supplementation and were asked to engage in regular weight-bearing exercise. Safety and efficacy are summarized for the initial 48 weeks of the trial. RESULTS: Grade 3 or higher abnormal laboratory values, signs, or symptoms developed in 5 of 32 (16%) participants on alendronate and 2 of 18 (11%) on placebo (P > .99). No cases of jaw osteonecrosis, atrial fibrillation, or nonhealing fractures were reported. Mean increases (95% confidence interval) in LS BMD over 48 weeks were significantly larger on alendronate (20% [14%-25%]) than placebo (7% [5%-9%]) (P < .001). Similar improvements were seen for whole body BMD. CONCLUSIONS: In this small study in children and adolescents perinatally infected with HIV with low LS BMD, 48 weeks of alendronate was well-tolerated, showed no safety concerns, and significantly improved LS and whole body BMD compared to participants on vitamin D/calcium supplementation and exercise alone. CLINICAL TRIALS REGISTRATION: NCT00921557.

FGF23-related hypophosphatemia in patients with low bone mineral density and fragility fractures: challenges in diagnosis and management.

PURPOSE: Hypophosphatemia (HP) can be observed in patients evaluated for skeletal fragility. We investigated prevalence of HP among outpatients referred for low bone density or fragility fractures, HP-associated clinical and biochemical features and outcomes of recommended diagnostic algorithm in our cohort. METHODS: Chronic HP (phosphate ≤ 2.7 mg/dL over 6 months or longer) was retrospectively investigated among 2319 patients. In renal wasting-related HP, intact FGF23 was assessed; non-suppressed FGF23 prompted the performance of 68Ga-DOTATOC PET/CT in the suspicion of tumor-induced steomalacia (TIO). RESULTS: Renal wasting-related HP (median 2.2, range 1.6-2.6 mg/dL) was observed in 19 patients (0.82%). FGF23 levels were suppressed in two patients diagnosed with renal tubular disease, increased in one and within normal range in most patients. X-linked hypophosphatemic rickets was diagnosed in one woman. In the remaining 16 patients, highly prevalent fragility fractures (50%) and severely reduced bone mineral density were detected, though diagnostic criteria for osteomalacia were not fulfilled. 68Ga-PET was performed in nine patients and was positive in four. While intact FGF23 levels alone failed to differentiate PET's outcomes (positive: FGF23 median 70.5 pg/mL; negative: 52 pg/mL, P = 0.462), the coexistence of multiple biochemical and radiologic alterations performed better in prediction of PET's positivity. CONCLUSION: Mild, apparently unexplained HP is observed in 0.82% of patients with low bone density or fragility fractures. In asymptomatic patients with isolated mild hypophosphatemia, the probability of finding an underlying tumor disease is very low, and utility of extensive and expensive diagnostic workup should be carefully considered in this setting.

Does cement augmentation of the screws in angular stable plating for proximal humerus fractures influence the radiological outcome: a retrospective assessment.

BACKGROUND: Screw-tip augmentation in angular stable plating offers new possibilities for the treatment of complex proximal humerus fractures. This retrospective analysis was performed to evaluate the radiological outcome of proximal humerus fractures treated with angular stable plates and additional screw-tip cement augmentation in patients over the age of 60. MATERIALS AND METHODS: A retrospective single centre analysis was conducted from June 2013 to December 2016. The minimum follow-up time was set to 6 months after surgery. Anatomical reduction and fixation were evaluated in respect to reattached tuberosities to the head fragment and the adequate restoration of the calcar area not showing any valgus or varus malalignment. Complete fracture healing was determined 3 months after surgery. Any failures such as secondary displacement, primary screw perforation, intraarticular cement leakage and avascular necrosis of the humeral head with concomitant screw cut-out were assessed. RESULTS: In total, 24 patients (21 females; 3 males) at a median age of 77.5 (62-96) years were included. Five 2-part, twelve 3-part and seven 4-part fractures were detected. The measured median BMD value of 23 patients was 78.4 mg/cm3 (38.8-136.9 mg/cm3). Anatomical reduction was achieved in 50% of the patients. In most cases, the A level screws and the B1 screw were augmented with bone cement by a median of 7 (5-9) head screws used. Postoperative varus displacement was not detected in any of the patients. One patient (4.2%) sustained an early secondary displacement. Intraarticular cement leakage was detected in 3 patients (2 head-split fractures). Avascular necrosis of the humeral head was observed in 4 patients (16.7%). Revision surgery was necessary in four cases, using hemiarthroplasty twice and reverse shoulder arthroplasty the other two times. CONCLUSION: Screw-tip augmentation in angular stable plating for proximal humerus fracture treatment showed a low secondary displacement rate of 4.2% in patients suffering from poor bone quality. Nevertheless, the occurrence of avascular necrosis of the humeral head with mainly severe fracture patterns observed in this study was higher compared to previously reported results in the literature. Cement augmentation in head-split fractures is not recommended, considering the high risk of an intraarticular cement leakage.

Bone health and its association with vitamin D and other covariates: A community-based study among women in a rural area of West Bengal.

BACKGROUND: Low bone mineral density (BMD) is implicated in the pathogenesis of osteoporosis and osteopenia, and primarily manifest as fragile bones. This is a rapidly emerging global health problem with increasing prevalence in India. OBJECTIVES: The objective of this was to assess the status of bone health and find its determinants among women aged 40 years and above in a rural population of West Bengal. METHODS: A community-based cross-sectional study was conducted from May 2017 to April 2018 among 260 women aged 40 years and above residing in the selected villages of Singur through multistage random sampling. Each respondent was interviewed using a structured schedule. Serum Vitamin D and calcium levels were investigated. BMD was assessed through calcaneal quantitative ultrasound. Osteoporosis was diagnosed among those with T-score ≤-2.5, while those with 25(OH) Vitamin D <30 ng/ml were classified to have Vitamin D insufficiency (VDI). Individuals with BMD T-score <-1 were considered to have low BMD. Inferential statistics were employed to find the associates of poor bone health. RESULTS: Out of 260 participants, 34 (13.1%) were screened positive for osteoporosis and 77.7% had low BMD. Approximately 75% had VDI. On multivariable analysis, VDI (adjusted odds ratio [95% confidence interval] = 4.13 [2.12, 8.37]) was a significant predictor of low BMD after adjustment for poor education, decreasing diet score, menopause, presence of comorbidity, underweight, and overweight explaining 43.6% of the variance. CONCLUSION: Serum Vitamin D levels are implicated to play a crucial role in bone metabolism; however, its effect on the body in accordance with other important hormones should be explored.

Low bone mineral density and renal malformation in Mexican patients with Turner syndrome are associated with single nucleotide variants in vitamin D-metabolism genes.

Turner syndrome (TS) is a common genetic disorder. TS-phenotype includes short stature, gonadal dysgenesis, cardiac and kidney malformations, low bone mineral density (low-BMD) and thyroiditis. TS-phenotype varies from patient to patient and the cause is not clear, the genomic background may be an important contributor for this variability. Our aim was to identify the association of specific single nucleotide variants in the PTPN22, VDR, KL, and CYP27B1 genes and vitamin D-metabolism, heart malformation, renal malformation, thyroiditis, and low-BMD in 61 Mexican TS-patients. DNA samples were genotyped for SNVs: rs7975232 (VDR), rs9536282 (KL), rs4646536 (CYP27B1), and rs1599971 (PTPN22) using the KASP assay. Chi-square test under a recessive model and multifactorial dimensionality reduction method were used for analysis. We found a significant association between renal malformation and the rs9536282 (KL) variant and between rs4646536 (CYP27B1) and low-BMD, these variants may have modest effects on these characteristics but contribute to the variability of the TS phenotype. In addition, we identified gene-gene interactions between variants in genes KL, CYP27B1 and VDR related to vitamin D-metabolism and low-BMD in TS-patients. Our results support the idea that the genetic background of TS-patients contributes to the clinical variability seen in them.

Low bone mineral density and associated factors in patients with haemophilia in Colombia.

INTRODUCTION: Patients with haemophilia may have lower levels of bone mineral density (BMD) compared with the general population. Moreover, haemophilic patients have increased risk factors for low bone mineral density (LBMD) such as arthropathy and resulting immobility, increasing their risk for osteoporosis and fractures. AIM: To assess the prevalence of LBMD and associated risk factors among a group of Colombian haemophilic patients. METHODS: In this case-control study, 90 patients with haemophilia A and B, over the age of five, were recruited. Controls were healthy participants matched by age, gender, body mass index (BMI), socioeconomic status, and race. All participants underwent dual energy X-ray absorptiometry (DXA) and the Global Physical Activity Questionnaire. Blood tests were collected to evaluate LBMD determinants in cases. RESULTS: BMD was lower in cases than in the control group. BMD of femoral necks was 0.907 g/cm2 in cases vs. 1.020 g/cm2 in controls (P = .019), and BMD of hips 0.930 g/cm2 in cases vs. 1030 g/cm2 in controls (P = .019). The greater the severity of haemophilia, the lower BMD in spine, femoral neck, and hips. Elevated C-protein levels were found in 44.1% of patients with LBMD and 14.8% with normal BMD (P = .003). The study found an adjusted prevalence ratio of 2.11, indicating that haemophilic patients are two times more likely to have LBMD (CI95% = 1.43-3.11 P < .001). CONCLUSION: Results from the present study showed that haemophilia was associated with a higher frequency of LBMD. Severity of haemophilia, haemophilic arthropathy, and elevated C-reactive protein levels was directly associated with LBMD.

Restrictive Eating Disorders and Skeletal Health in Adolescent Girls and Young Women.

This article reviews the effects of restrictive eating disorders on bone health. The relationship between eating disorders and amenorrhea is discussed in detail. The pathologic impact of malnutrition on bone is explored by examining the results of studies using various available imaging techniques. The multiple hormonal alterations seen in adolescents and young women with anorexia nervosa are reviewed, as well as how these alterations may influence bone turnover, density, structure, and strength. The diagnostic clinical evaluation for adolescents and young women with these disorders is also outlined. Available treatment options, including those that hold promise for efficacy, as well as those we deemed to be ineffective, are considered from both the clinical and mechanistic standpoints. Finally, future research opportunities are offered, including intriguing work in the area of fat and bone interactions.

Vitamin D, osteoprotegerin/receptor activator of nuclear factor-kappaB ligand (OPG/RANKL) and inflammation with alendronate treatment in HIV-infected patients with reduced bone mineral density.

OBJECTIVES: The aim of the study was to determine the effect of alendronate (ALN) on inflammatory markers and osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL), and to explore the associations of baseline systemic inflammation and vitamin D status on the bone mineral density (BMD) response to ALN. METHODS: Eighty-two HIV-positive patients with lumbar spine T-score ≤ -1.5 were randomized to ALN 70 mg weekly or placebo for 48 weeks; all received calcium carbonate 500 mg/vitamin D3 200 IU twice daily. Serum C-telopeptide (CTx) and BMD were assessed at baseline and week 48. Stored plasma samples in 70 subjects were assayed for levels of 25-hydroxyvitamin D (25(OH)D), OPG, RANKL, interleukin (IL)-6 and soluble receptors for tumour necrosis factor (TNF)-α 1 and 2 (sTNFR 1 and 2). RESULTS: ALN increased BMD more than placebo at both the lumbar spine (difference ALN - placebo 2.64%; P = 0.011) and the total hip (difference 2.27%; P = 0.016). No within- or between-arm differences in OPG, RANKL or inflammatory markers were observed over 48 weeks. High baseline CTx and sTNFR2 were associated with a more robust BMD response to ALN over 48 weeks at the lumbar spine [difference 5.66%; 95% confidence interval (CI) 3.50, 7.82; P < 0.0001] and total hip (difference 4.99%; 95% CI 2.40, 7.57; P = 0.0002), respectively. Baseline 25(OH)D < 32 ng/mL was associated with larger increases in total hip BMD over 48 weeks, independent of ALN treatment (P = 0.014). CONCLUSIONS: Among HIV-positive patients, higher baseline bone resorption and TNF-α activity were associated with an increased BMD response to ALN. The greater BMD response in those with lower vitamin D reinforces the importance of vitamin D supplementation with bisphosphonate treatment.

Z-score discordance and contributing factors in healthy premenopausal women with low bone mineral density: the Korean National Health and Nutrition Examination Survey 2008-9.

The premenopausal period is important for bone health and prevention of future fractures, but measuring bone mineral density (BMD) at only one site may not be sufficient to determine therapeutic strategies for low BMD in premenopausal women due to the presence of Z-score discordance. In this study, we investigated Z-score discordance in addition to contributing factors of idiopathic low BMD in healthy premenopausal Korean women. We studied 3003 premenopausal women aged 18-50 years, without secondary causes for low BMD and history of fragility fracture, who had participated in the Fourth Korean National Health and Nutrition Examination Surveys (2008-2009). Low body mass index (BMI), low vitamin D level, and low body muscle mass were associated with low BMD even in premenopausal women. Risk factors differed depending on the anatomic site. Low BMI and low vitamin D level were risk factors for low femoral neck BMD (FN-BMD), but not for low lumbar spine BMD (LS-BMD). Only total muscle mass had a slight effect on low LS-BMD. Z-score discordance was much higher than expected, in 75 and 73.8 % of the low LS-BMD and low FN-BMD groups, respectively. Our findings suggest the need to consider BMD discordance in premenopausal women and also to provide information on correctable factors affecting low BMD in younger populations. Long-term follow-up is needed to evaluate the possible effect of Z-score discordance on the prognosis of osteoporosis and subsequent fracture risk.

Female Athlete Triad: Past, Present, and Future.

After the passage of Title IX in 1972, female sports participation skyrocketed. In 1992, the female athlete triad was first defined; diagnosis required the presence of an eating disorder, amenorrhea, and osteoporosis. However, many athletes remained undiagnosed because they did not meet all three of these criteria. In 2007, the definition was modified to a spectrum disorder involving low energy availability (with or without disordered eating), menstrual dysfunction, and low bone mineral density. With the new definition, all three components need not be present for a diagnosis of female athlete triad. Studies using the 1992 definition of the disorder demonstrated a prevalence of 1% to 4% in athletes. However, in certain sports, many female athletes may meet at least one of these criteria. The actual prevalence of athletes who fall under the "umbrella" diagnosis of the female athlete triad remains unknown.