Spine Areal Bone Mineral Density Research Articles

Associations of Serum Irisin and Fibroblast Growth Factor-21 Levels With Bone Mineral Characteristics in Eumenorrheic Adolescent Athletes With Different Training Activity Patterns.

To describe serum irisin and fibroblast growth factor-21 (FGF-21) concentrations in healthy female adolescents with different training activity patterns and their associations with bone mineral properties and metabolic markers. A total of 62 adolescent girls aged 14-18years were recruited: 22 rhythmic gymnasts, 20 swimmers, and 20 untrained controls. Bone mineral characteristics by dual-energy X-ray absorptiometry, daily energy intake by dietary recall, serum irisin, FGF-21, undercarboxylated osteocalcin, and C-terminal telopeptide of type I collagen were measured in all girls. Whole body and lumbar spine areal bone mineral density and lumbar spine bone mineral content were higher in the rhythmic gymnasts group compared with swimmers and untrained controls groups (P < .05). Serum irisin, FGF-21, undercarboxylated osteocalcin, and C-terminal telopeptide of type I collagen levels were not significantly different between the groups. In the rhythmic gymnasts group, serum FGF-21 concentration was positively correlated with lumbar spine areal bone mineral density independently of confounding factors (r = .51; P = .027). Serum irisin and FGF-21 levels were not different between adolescent eumenorrheic girls with different training activity patterns. FGF-21 was positively associated with lumbar spine areal bone mineral density, which predominantly consists of trabecular bone in adolescent rhythmic gymnasts.

Risk Factors Associated with Incident Vertebral Fractures in Steroid-treated Males with Duchenne Muscular Dystrophy.

Prevention of fractures is an unmet need in glucocorticoid (GC)-treated Duchenne muscular dystrophy. This study explored factors associated with incident vertebral fractures (VFs) to inform future fracture prevention efforts. VFs were evaluated prospectively at study baseline and 12 months on lateral spine radiographs in participants aged 4 to 25 years with Duchenne muscular dystrophy. Clinical factors were analyzed for their association with the change in Spinal Deformity Index (sum of the Genant-defined VF grades from T4 to L4) between baseline and 12 months. Thirty-eight males were evaluated (mean ± SD age at baseline 11.0 ± 3.6 years; mean ± SD GC duration at baseline 4.1 ± 3.1 years; 74% ambulatory). Nine of 38 participants (24%) had 17 incident VFs, of which 3/17 VFs (18%) were moderate/severe. Participants with 12-month incident VF had lower mean ± SD baseline lumbar spine areal bone mineral density Z-scores (-2.9 ± 1.0 vs -1.9 ± 1.1; P = .049) and lower total body less head areal bone mineral density Z-scores (-3.1 ± 1.2 vs -1.6 ± 1.7; P = .036). Multivariable linear regression showed that at least 1 VF at baseline (P < .001), a higher number of antecedent non-VF (P < .001), and greater bone age delay at baseline (P = .027) were significant predictors of an increase in the Spinal Deformity Index from baseline to 12 months. The observation that ≥ 1 prevalent VF and/or non-VF were the strongest predictors of incident VFs at 12 months supports the need for prevention of first fractures in this high-risk setting. Bone age delay, a marker of GC exposure, may assist in the prioritization of patients in efforts to prevent first fractures.

Much lower prevalence and severity of spine degenerative changes among older Chinese women than among older Caucasian women and its implication for the interpretation of lumbar spine BMD T-score for Chinese women.

The prevalence and severity of spine degenerative changes have been noted to be lower among older Chinese women than among older Caucasian women. Spine degenerative changes associated with marginal osteophytosis, trabecular thickening, subchondral sclerosis, facet joint arthrosis, and disc space narrowing can all lead to artificially higher spine areal bone mineral density (BMD). The lower prevalence and severity of spine degeneration have important implications for the interpretation of spine areal BMD reading for Chinese women. With fewer contributions from spine degenerative changes, following natural aging, the declines of population group means of spine BMD and T-score are faster for Chinese women than for Caucasian women. While a cutpoint T-score ≤ -2.5 for defining spine densitometric osteoporosis is recommended for Caucasian women, for Chinese women the same cutpoint T-score of ≤ -2.5 inflates the estimated osteoporosis prevalence based on spine BMD measure. In addition to the use of an ethnicity-specific BMD reference database, a stricter cutpoint T-score for defining spine densitometric osteoporosis among older Chinese women should be applied.

Follistatin Is Associated with Bone Mineral Density in Lean Adolescent Girls with Increased Physical Activity.

Follistatin is a member of the activin-follistatin-inhibin hormonal system and is proposed to affect bone metabolism. However, data regarding the effect of follistatin on bone are relatively scarce and contradictory in humans. The purpose of the current study was to investigate possible associations of serum follistatin concentration with bone mineral characteristics in lean and physically active adolescent girls. Bone mineral density, body composition, resting energy expenditure and different energy homeostasis hormones in serum including follistatin, leptin and insulin were investigated. Significant relationships (p < 0.05) between serum follistatin (1275.1 ± 263.1 pg/mL) and whole-body (WB) bone mineral content (r = 0.33), WB areal bone mineral density (aBMD) (r = 0.23) and lumbar spine (LS) aBMD (r = 0.29) values were observed. Serum follistatin remained associated with LS aBMD independent of body fat and lean masses (r = 0.21; p < 0.05). However, the follistatin concentration explained only 3% (R2 × 100; p = 0.049) of the total variance in LS aBMD values. In conclusion, serum follistatin concentrations were associated with bone mineral values in lean adolescent girls with increased physical activity. Follistatin was an independent predictor of lumbar spine areal bone mineral density, which predominantly consists of trabecular bone.

Associations of body mass index, body fat percentage and sarcopenia components with bone health estimated by second-generation high-resolution peripheral quantitative computed tomography in older adults with obesity

PurposeTo investigate associations between body mass index (BMI), body fat percentage, and components of sarcopenia (muscle mass and muscle strength/power), with bone microarchitecture measured by high-resolution peripheral computed tomography (HR-pQCT) in older adults with obesity. MethodsSeventy-four adults aged ≥ 55 years with body fat percentage ≥ 30 % (men) or ≥40 % (women) were included. Fat mass, lean mass and total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD) were measured by dual-energy X-ray absorptiometry. Appendicular lean mass (ALM) was calculated as the sum of lean mass in the upper- and lower-limbs. BMI was calculated and participants completed physical function assessments including stair climb power test. Distal tibial bone microarchitecture was assessed using HR-pQCT. Linear regression (β-coefficients and 95 % confidence intervals) analyses were performed with adjustment for confounders including age, sex, smoking status, vitamin D and self-reported moderate to vigorous physical activity. ResultsBMI and ALM/height2 were both positively associated with total hip, femoral neck and lumbar spine aBMD and trabecular bone volume fraction after adjusting for confounders (all p < 0.05). Body fat percentage was not associated with aBMD or any trabecular bone parameters but was negatively associated with cortical area (p < 0.05). Stair climb power (indicating better performance) was positively associated with cortical area and negatively associated with bone failure load (both p < 0.05). ConclusionHigher BMI, ALM/height2 and muscle power were associated with more favourable bone microarchitecture, but higher body fat percentage was negatively associated with cortical bone area. These findings suggest that high BMI may be protective for fractures and that this might be attributable to higher muscle mass and/or forces, while higher relative body fat is not associated with better bone health in older adults with obesity.

The Influence of Accelerometer Epoch Length on Associations of Physical Activity Intensity and Volume with Bone Outcomes.

Two accelerometer metrics (intensity-gradient and average-acceleration) can be used to determine the relative contributions of physical activity (PA) volume and intensity for health, but it is unknown whether epoch length influences the associations detected. This is important when considering bone health, as bone is particularly responsive to high intensity PA, which may be underestimated by longer epochs. This study aimed to assess the associations between average-acceleration, a proxy measure of PA volume, and intensity-gradient, reflective of PA intensity distribution, from PA data from 1-s to 60-s epochs at age 17 to 23 years with bone outcomes at age 23 years. This is a secondary analysis of 220 participants (124 females) from the Iowa Bone Development Study, a longitudinal study of bone health from childhood to early adulthood. Accelerometer-assessed PA data, captured at age 17 to 23 years, were summarised over 1-s, 5-s, 15-s, 30-s, and 60-s epochs, to generate average-acceleration and intensity-gradient from each epoch length, averaged across ages. Regression analysed associations between mutually adjusted average-acceleration and intensity-gradient with dual-energy X-ray absorptiometry assessed total-body-less-head (TBLH) bone mineral content (BMC), spine areal bone mineral density (aBMD), hip aBMD, and femoral neck cross-sectional area and section modulus at age 23 years. Intensity-gradient was positively associated with TBLH BMC in females, with spine aBMD in males, and with hip aBMD and geometry in both sexes, when a 1 to 5-s epoch was used. Average-acceleration was positively associated with TBLH BMC, spine aBMD and hip aBMD in males, generally when the adjustment for intensity-gradient was from > 1-s epochs. Intensity and volume were important for bone outcomes in both sexes and males, respectively. A 1 to 5-s epoch length was most appropriate to assess the mutually adjusted associations of intensity-gradient and average-acceleration with bone outcomes in young adults.

Skeletal Microstructure in Caribbean Hispanic Women.

Hispanic individuals are underrepresented in skeletal research. Bone mineral density (BMD) and fracture data are conflicting. We investigated skeletal health in elderly Caribbean Hispanic (HW), non-Hispanic white (NHW), and non-Hispanic black (NHB) women in a population-based study in New York City. We utilized high-resolution peripheral quantitative CT (HRpQCT), dual-energy X-ray absorptiometry (DXA), and finite element analysis (FEA). Of 442, 48.4% were HW, 21.3% NHW, and 30.3% NHB. Adjusted analyses are shown. Compared to NHW, HW had 8.5% (p < 0.01) lower spine areal BMD (aBMD) and 5.1% lower trabecular bone score (TBS). The frequency of morphometric vertebral fractures did not differ between HW and NHW. By HRpQCT, HW had 2.9% higher cortical (Ct) volumetric BMD (vBMD), 7.9% greater Ct area (Ct.Ar) and 9.4% greater Ct thickness (Ct.Th) at the radius compared to NHW. Results were similar at the tibia but trabecular microstructure tended to be worse. Ultimately, failure load (FL) did not differ between HW and NHW at either site. aBMD was 3.8% to 11.1% lower at the spine, femoral neck, and radius in HW compared to NHB (all p < 0.001) and vertebral fractures were twice as common. Compared to NHB, HW had 7.7% to 10.3% lower Ct.Ar at both the radius and tibia as well as 8.4% lower total vBMD, 6.3% lower trabecular number, and 10.3% lower Ct.Th at the tibia associated with 18.2% and 12.5% lower FL at both sites, respectively. In conclusion, HW had lower spine aBMD and TBS versus NHW women, whereas microstructural differences at the radius and tibia were small and not associated with differences in FL. In contrast, HW had lower aBMD, as well as deteriorated radial and tibial microstructure associated with worse FL compared to NHB women. Our results provide insight into racial/ethnic differences in skeletal health, adding to data that may be used to improve osteoporosis screening and treatment in HW. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Safety and Efficacy of Alendronate to Treat Osteopenia in Children During Therapy for Acute Lymphoblastic Leukemia: A Retrospective Cohort Study of Sequential Outcomes.

Low bone mineral density is encountered in children with acute lymphoblastic leukemia (ALL) before, during, and after treatment. Prior experience with alendronate, an oral bisphosphonate, demonstrated high tolerability and evident clinical efficacy. However, concerns have been expressed about the long-term safety and utility of such agents in children. Sixty-nine children with ALL received alendronate for a mean of 87 weeks after dual-energy radiograph absorptiometry. Dual-energy radiograph absorptiometry was repeated following the completion of alendronate, and 5 to 9 years later in a subgroup of 32 children. Lumbar spine areal bone mineral density (LS aBMD) Z scores were obtained. The mean LS aBMD Z score rose from -1.78 to-0.47 ( P <0.0001). There was a modest median loss of LS aBMD subsequently in the 32 subjects on long-term follow-up. Almost 80% (N=172) of the children remain in continuous complete remission at a mean of 14.5 years from diagnosis. Of those who received alendronate, which was almost uniformly well tolerated, 7/69 (10.3%) relapsed compared with 19/89 (21.3%) who did not receive the drug. Alendronate appears to be well tolerated and moderately effective in osteopenic children with ALL. Whether it offers protection against relapse of leukemia needs further study.

Prevalence of Vertebral Fractures and Non-fracture Deformities in Healthy Adult Men: The Importance of Morphologic Criteria.

Vertebral fractures (VF) are common in older men but data on VF prevalence in young men is limited. The aim of this study was to describe the prevalence of VF and non-fracture vertebral deformities (VD) in healthy young to middle-aged men, and compare the characteristics of men with normal vertebrae, VF and VD. In this cross-sectional study, vertebral fracture assessment by dual-energy X-ray absorptiometry was performed in 650 men, aged 32 to 60years (mean 46.2), from the population-based SIBLOS-SIBEX cohort. For VF and VD assessment, both the modified algorithm-based qualitative approach (morphologic criteria) to discriminate VF from VD and the semi-quantitative (morphometric) grading system of Genant (GSQ) were used. We found 48 (0.6%) fractured vertebrae, of which 15 were classified grade 1, 29 grade 2 and 4 grade 3 VF. There were 378 (4.7%) VD, of which 296 were scored grade 1, 82 grade 2 and none grade 3 VD. Twenty-six participants (4%) had VF, 15 had one and 11 had 2 or more VF. Two hundred and twenty-eight (35.1%) men had VD. Femoral neck, total hip and lumbar spine areal bone mineral density (aBMD) were lower in men with VF than in those with normal vertebrae or VD. Men with VD, in turn, had aBMD values similar to men with normal vertebrae. Our results suggest that -even in young healthy men-using the GSQ without taking qualitative aspects into account overestimates VF prevalence, confirming the importance of morphologic criteria to correctly diagnose and distinguish VF from VD.

Oral Contraceptives and Female Rowers' Skeletal Health.

Redinger, AL and Baker, BS. Oral contraceptives and female rowers' skeletal health. J Strength Cond Res 37(3): 669-677, 2023-Previous studies suggest that women using oral contraceptives (OC) experience fewer skeletal benefits from exercise compared with non-OC users. These findings may be especially important for athletes competing in weight-supported sports with a high prevalence of low bone mineral density and fracture, such as rowing. The purpose of this study was to examine skeletal health and bone injuries in collegiate female rowers. Forty-nine National Collegiate Athletic Association Division I female rowers completed general health, menstrual history, and bone physical activity questionnaire (BPAQ) surveys. Dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) scans were used to assess bone content, density, and geometry. Contraceptive (OC users n = 14, non-OC users n = 35) and self-reported stress fracture (SFx n = 11, None n = 38) groups were analyzed using analysis of covariance and independent t -tests. Additionally, effect sizes ( d ) were calculated and significance was set at p ≤ 0.05. Oral contraceptive users had reduced lumbar spine areal bone mineral density after adjustment for Total BPAQ ( d = 0.58; p = 0.041) compared with non-OC users, but all other total body and site-specific DXA measures of bone mineral content and density were similar between contraceptive and injury groups. When comparing bone geometry of the 4, 38, and 66% tibiae using pQCT, no significant differences were found after adjustment for either contraceptive or injury group (all p > 0.060). Our findings suggest that OC usage was not associated with reduced skeletal health in competitive female rowers as evidenced by all Z-scores being above -2.0 and similar bone indices of mineralized content, density, geometry, and estimated strength between the groups.

Bone marrow transplantation as a therapy for autosomal dominant osteopetrosis type 2 in mice.

Autosomal dominant osteopetrosis type II (ADO2) is a heritable bone disease of impaired osteoclastic bone resorption caused by missense mutations in the chloride channel 7 (CLCN7) gene. Clinical features of ADO2 include fractures, osteomyelitis of jaw, vision loss, and in severe cases, bone marrow failure. Currently, there is no effective therapy for ADO2, and patients usually receive symptomatic treatments. Theoretically, bone marrow transplantation (BMT), which is commonly used in recessive osteopetrosis, could be used to treat ADO2, although the frequency of complications related to BMT is quite high. We created an ADO2 knock-in (p.G213R mutation) mouse model on the 129 genetic background, and their phenotypes mimic the human disease of ADO2. To test whether BMT could restore osteoclast function and rescue the bone phenotypes in ADO2 mice, we transplanted bone marrow cells from 6-8 weeks old male WT donor mice into recipient female ADO2 mice. Also, to determine whether age at the time of transplant may play a role in transplant success, we performed BMT in young (12-week-old) and old (9-month-old) ADO2 mice. Our data indicate that ADO2 mice transplanted with WT marrow achieved more than 90% engraftment up to 6 months post-transplantation at both young and old ages. The in-vivo DXA data revealed that young ADO2 mice transplanted with WT marrow had significantly lower whole body and spine areal bone mineral density (aBMD) at month 6 post-transplantation compared to the ADO2 control mice. The old ADO2 mice also displayed significantly lower whole body, femur, and spine aBMD at months 4 and 5 post-transplantation compared to the age-matched control mice. The in-vivo micro-CT data showed that ADO2 experimental mice transplanted with WT marrow had significantly lower BV/TV at months 2 and 4 post-transplantation compared to the ADO2 control mice at a young age. In contrast, ADO2 control and experimental mice displayed similar BV/TV values for all post-transplantation time points at old age. In addition, serum CTX was significantly higher at month 2 post-transplantation in both young and old ADO2 experimental mice compared to the ADO2 control mice. Serum P1NP levels in young ADO2 experimental mice were significantly higher at baseline and month 2 post-transplantation compared to the ADO2 control mice. These data suggest that BMT may provide, at least, some beneficial effect at both young and adult ages.

Bone accrual and structural changes over one year in youth with cystic fibrosis

BackgroundPediatric bone accrual governs peak bone mass and strength. Longitudinal studies of bone health in youth with cystic fibrosis (CF) may provide insight into CF-related bone disease (CFBD), a prevalent co-morbidity in adults with CF. MethodsThis one-year longitudinal study of youth with pancreatic insufficient CF, enrolled in a nutrition intervention study [n = 62 (36 M/26F)] 1) examined dual-energy x-ray absorptiometry (DXA)-defined lumbar spine (LS) and total body less head (TBLH) bone accrual and 2) compared their changes in peripheral quantitative computed tomography (pQCT) cortical and trabecular tibial bone density and geometry to those of a healthy reference group [n = 143 (68 M/75F)].Main outcome measures were 1) DXA: lumbar spine areal bone mineral density (LSaBMD) and total body less head bone mineral content (TBLH-BMC), sex- and pubertal status-specific, height velocity (HV)-adjusted or HV and lean body mass velocity (HV-LBMV)-adjusted annualized velocity-Z scores and 2) pQCT: age, sex, pubertal status and, when appropriate, tibial length adjusted Z-scores for bone architecture measures.DXA velocity-Z were compared to expected mean of 0 and correlations with clinical parameters (age, BMI-Z and FEV1%-predicted) tested. Within-subject comparisons of HV-adjusted and LBMV-HV-adjusted DXA velocity-Z were conducted in CF.pQCT Z-scores were compared between the two groups over one year using longitudinal models. Longitudinal relationships between measures of bone health and clinical parameters (age, BMI-Z and FEV1%-predicted) were examined in individuals with CF. ResultsDXA velocity-Z were higher than normal in females (p < 0.05) but not males with CF. HV-adjusted and LBMV-HV-adjusted velocity-Z did not differ for LSaBMD or TBLH-BMC.In males with CF, both HV-adjusted and LBMV-HV-adjusted LSaBMD velocity-Z scores correlated negatively with age (HV rho: −0.35; p = 0.045 and LBMV-HV rho: −0.47; p = 0.0046). In males with CF BMI-Z correlated positively with HV-adjusted LSaBMD velocity-Z (rho: 0.37; p = 0.034), but this relationship did not persist for LBMV-HV (rho: 0.14; p = 0.42). In females with CF, no correlations between LSaBMD velocity-Z scores and age or BMI-Z were found (all p > 0.05). No correlations between LSaBMD velocity-Z scores and FEV1%-predicted were seen in either sex (all p > 0.12). TBLH-BMC velocity Z-scores were not correlated with clinical parameters in either sex (all p > 0.1).At baseline, multiple pQCT parameters were lower in CF (p < 0.05). pQCT Z-scores did not differ between baseline and one-year in either CF or reference group. In a longitudinal model comparing pQCT-Z changes in CF and reference, multiple pQCT-Z outcomes remained lower in CF, but the changes in parameters did not differ in CF vs reference (all p > 0.26). Lower pQCT outcomes in CF were largely restricted to males (CF group*female sex interaction beta coefficients > 0). In this combined longitudinal model, of both CF and reference, BMI-Z was positively associated with pQCT-Z parameters(p < 0.001).Multiple pQCT-Z outcomes positively correlated with both BMI-Z and FEV1%-predicted in males with CF, and with FEV1%-predicted in females with CF (p < 0.05). Age was negatively associated with section modulus (p = 0.001) in males and with cortical density-Z in females (p < 0.001). ConclusionsWith improved longevity, bone health in CF is of increasing importance. On average, bone accrual was preserved in youth with CF, and while deficits in bone geometry and strength were found, these deficits did not worsen over the one-year study. Lower LS bone accrual with increasing age suggests emerging adulthood is a period of vulnerability in CF while the role of LBM in bone health is underscored by the lack of relationship between LBMV-adjusted accrual and BMI. These findings may be useful in targeting screening practices and interventions.

Skeletal status in children and adolescents with new-onset type 1 diabetes: a preliminary study based on bone densitometry and quantitative ultrasound.

Type 1 diabetes (T1D) represents a risk factor for bone loss and impaired bone quality. We conducted an exploratory retrospective cross-sectional study involving youths with new-onset T1D, to investigate the relationship between lumbar spine dual-energy X-ray absorptiometry (DXA) and phalangeal quantitative ultrasound (QUS) measurements, along with their correlation with markers of bone turnover, glucose homeostasis, and residual β-cell function. 17 children and adolescents (8 females) with recent-onset T1D were enrolled into this study. Lumbar spine areal bone mineral density (aBMD) and age-adjusted amplitude-dependent speed of sound (AD-SoS) Z-scores were indicative of low BMD status (≤ -2.0 SD) in 11.7% and 17.6% of participants, respectively. Spearman's correlation analysis revealed significant inverse correlations between AD-SoS values and circulating levels of β-CrossLaps, alkaline phosphatase, and osteocalcin, along with a significant positive correlation between bone transmission time (BTT) values and fasting plasma C-peptide (FCP) levels. There was no statistically significant correlation between DXA-QUS parameters, fasting plasma glucose (FPG), and glycated haemoglobin (HbA1c). Finally, there was a significant positive correlation between lumbar spine aBMD and BTT values. Our study suggests that DXA and/or QUS parameters may be altered in a small proportion of T1D children and adolescents at the disease onset. Additionally, residual β-cell function may represent a protective factor against T1D-related detrimental skeletal changes. Large and long-term prospective studies are needed to confirm these preliminary findings since the present study is limited by the retrospective cross-sectional design and by its small sample size.

Case Report: Low Bone and Normal Lean Mass in Adolescents With Complete Androgen Insensitivity Syndrome

IntroductionOsteopenia and osteoporosis have been reported in adults with Complete Androgen Insensitivity Syndrome (CAIS). Little is known about changes in bone mineral density (BMD) in adolescents with CAIS and whether it is affected by early gonadectomy. Body composition data have not been reported.MethodsSingle-center, retrospective study of CAIS adolescents who underwent dual-energy x-ray absorptiometry (DXA) (Hologic, Horizon A). Body composition is presented as lean and fat mass indices (LMI, FMI). Z-scores for lumbar spine areal BMD (LBMD), total body less head (TBLH), bone mineral content (BMC), LMI, and FMI were calculated using female normative data. Results are expressed as median and min, max.ResultsSix females with genetically confirmed CAIS were identified—one with intact gonads and five with history of gonadectomy at 2–11 months. In the subject with intact gonads, LBMD-Z and TBLH BMC-Z were −1.56 and −1.26, respectively, at age 16 years. Among those with gonadectomy, LBMD-Z was −1.8 (−3.59 to 0.49) at age 15.6 years (12–16.8) and decreased in all three subjects who had longitudinal follow-up despite hormone replacement therapy (HRT). Adherence to HRT was intermittent. LMI-Z and FMI-Z were 0.1 (−1.39 to 0.7) and 1.0 (0.22 to 1.49), respectively.ConclusionsThese limited data indicate that adolescents with CAIS have bone mass deficit. Further studies are needed to understand the extent of BMD abnormalities and the effect of gonadectomy, especially early in childhood, and to establish the optimal HRT regimen for bone accrual. Data on lean mass are reassuring.

Musculoskeletal Responses to Exercise Plus Nutrition in Men with Prostate Cancer on Androgen Deprivation: A 12-Month RCT.

Androgen deprivation therapy (ADT) for prostate cancer has multiple adverse effects on musculoskeletal health. This 12-month randomized controlled trial aimed to assess the effects of multicomponent exercise training combined with whey protein, calcium and vitamin D supplementation on bone mineral density (BMD), structure and strength, body composition, muscle strength, and physical function in ADT-treated men. Seventy ADT-treated men were randomized to exercise plus supplementation (Ex + Suppl; n = 34) or usual care (control; n = 36). Ex + Suppl involved thrice weekly progressive resistance training plus weight-bearing impact exercise with daily multinutrient supplementation. Primary outcomes were DXA hip and spine areal BMD. Secondary outcomes included the following: tibia and radius pQCT volumetric BMD, bone structure and strength, DXA body composition, pQCT muscle and fat cross-sectional area and muscle density, and muscle strength and physical function. Sixty men (86%) completed the study. Mean exercise and supplement adherence were 56% and 77%, respectively. There were no effects of the intervention on bone or body composition outcomes. Ex + Suppl improved leg muscle strength (net difference, (95% confidence interval, or CI), 14.5% (-0.2 to 29.2); P = 0.007) and dynamic mobility (four-square-step test time, -9.3% (-17.3 to -1.3), P = 0.014) relative to controls. Per-protocol analysis of adherent participants (≥66% exercise, ≥80% supplement) showed Ex + Suppl preserved femoral neck aBMD (1.9% (0.1 to 3.8), P = 0.026) and improved total body lean mass (1.0 kg (-0.23 to 2.22), P = 0.044) relative to controls. Exercise training combined with multinutrient supplementation had a limited effect on ameliorating the adverse musculoskeletal consequences of ADT, likely related to the modest intervention adherence.

Trabecular Bone Score Reference Values for Children and Adolescents According to Age, Sex, and Ancestry.

Trabecular bone score (TBS) is used for fracture prediction in adults, but its utility in children is limited by absence of appropriate reference values. We aimed to develop reference ranges for TBS by age, sex, and population ancestry for youth ages 5 to 20 years. We also investigated the association between height, body mass index (BMI), and TBS, agreement between TBS and lumbar spine areal bone mineral density (aBMD) and bone mineral apparent density (BMAD) Z-scores, tracking of TBS Z-scores over time, and precision of TBS measurements. We performed secondary analysis of spine dual-energy X-ray absorptiometry (DXA) scans from the Bone Mineral Density in Childhood Study (BMDCS), a mixed longitudinal cohort of healthy children (n= 2014) evaluated at five US centers. TBS was derived using a dedicated TBS algorithm accounting for tissue thickness rather than BMI. TBS increased only during ages corresponding to pubertal development with an earlier increase in females than males. There were no differences in TBS between African Americans and non-African Americans. We provide sex-specific TBS reference ranges and LMS values for calculation of TBS Z-scores by age and means and SD for calculation of Z-scores by pubertal stage. TBS Z-scores were positively associated with height Z-scores at some ages. TBS Z-scores explained only 27% and 17% of the variance of spine aBMD and BMAD Z-scores. Tracking of TBS Z-scores over 6 years was lower (r= 0.47) than for aBMD or BMAD Z-scores (r= 0.74 to 0.79), and precision error of TBS (2.87%) was greater than for aBMD (0.85%) and BMAD (1.22%). In sum, TBS Z-scores provide information distinct from spine aBMD and BMAD Z-scores. Our robust reference ranges for TBS in a well-characterized pediatric cohort and precision error estimates provide essential tools for clinical assessment using TBS and determination of its value in predicting bone fragility in childhood and adolescence. © 2022 American Society for Bone and Mineral Research (ASBMR).

Altered cortical bone strength and lean mass in young women with long-duration (19\xa0years) type 1 diabetes

To investigate bone health and body composition in young women with long-duration type 1 diabetes (T1D) in relation to matched controls. Twenty-three Swedish women, age 19.2–27.9 years, with a T1D duration of 10 years or more were recruited from the Swedish National Diabetes Registry (NDR). An age-, gender- and geography-matched control group was recruited. Bone mass and body composition were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Data was retrieved from the NDR and SWEDIABKIDS registries. T1D individuals had a mean diabetes duration of 19 years. T1D individuals had reduced lean mass (40.0 ± 6.1 kg vs. 43.9 ± 4.9 kg) and were shorter (1.66 ± 0.06 m vs. 1.71 ± 0.06 m) although comparable BMI. Subjects with T1D had lower muscle area (P = 0.0045). No differences were observed for fractures; physical activity; total, lumbar spine or femur areal bone mineral density. The cortical bone strength strain index was lower for TD1 patients (1875 ± 399 mm3 vs. 2277 ± 332 mm3). In conclusion, young women with long-term diabetes duration showed reduced cortical bone strength, decreased periosteal circumference, endosteal circumference and altered body composition. These factors contribute to the health burden of TD1, which warrants further attention for advancing bone health in women with T1D.

Osteogenesis Imperfecta: Skeletal outcomes after bisphosphonate discontinuation at final height

Intravenous cyclical bisphosphonates are widely used to treat children with moderate to severe osteogenesis imperfecta (OI). Bisphosphonates are often discontinued when growth is completed, but subsequent skeletal changes have not been studied in detail. We assessed 31 patients (22 females) with OI who had started intravenous bisphosphonates (either pamidronate or zoledronic acid) before 13 years of age, were treated for at least 2 years (range 4.7-15.7 years), and discontinued treatment after completion of growth, when their age ranged from 13.4 to 20.0 years (mean 16.4 years). At 4 years after treatment discontinuation, lumbar spine areal bone mineral density (BMD) had increased by 4% (p < 0.05). Peripheral quantitative computed tomography of the radius showed a decrease in trabecular volumetric BMD at the distal metaphysis of 19% but an increase in cortical volumetric BMD of 4% (p < 0.05 for both). None of the patients sustained a new vertebral compression fracture during follow-up. The proportion of patients with new long-bone fractures was higher in the 2 years before treatment discontinuation than in the last 2 years of follow-up (42% and 16%, respectively; p < 0.05). © 2019 American Society for Bone and Mineral Research.

Sclerostin, preadipocyte factor-1 and bone mineral values in eumenorrheic adolescent athletes with different training patterns.

The specific aims of the study were to compare possible differences in sclerostin and preadipocyte factor-1 (Pref-1) between rhythmic gymnasts (RG), swimmers (SW) and untrained controls (UC), and to investigate the relationships of sclerostin and Pref-1 with bone mineral characteristics in studied groups. This study included 62 eumenorrheic adolescents (RG = 22; SW = 20; UC = 20). Bone mineral and body composition characteristics were measured by dual-energy X-ray absorptiometry, and sclerostin, Pref-1, osteocalcin and C-terminal telopeptide of type I collagen (CTx) were measured. Sclerostin was higher (P = 0.001) in RG (129.35 ± 51.01pg/ml; by 74%) and SW (118.05 ± 40.05pg/ml; by 59%) in comparison with UC (74.32 ± 45.41pg/ml), while no differences (P = 0.896) were seen in Pref-1 (RG: 1.42 ± 0.16ng/ml; SW: 1.41 ± 0.20ng/ml; UC: 1.39 ± 0.26ng/ml) between groups. Osteocalcin (RG: 7.74 ± 4.09ng/ml; SW: 8.05 ± 4.18ng/ml; UC: 7.04 ± 3.92ng/ml; P = 0.843) and CTx (RG: 0.73 ± 0.22ng/ml; SW: 0.64 ± 0.16ng/ml; UC: 0.62 ± 0.20ng/ml; P = 0.173) were not different between groups. Sclerostin correlated (P < 0.05) with whole-body bone mineral content (r = 0.61) and lumbar spine (LS) areal bone mineral density (aBMD) (r = 0.43) in RG, and femoral neck aBMD (r = 0.45) in UC. No correlation was found between sclerostin and bone mineral values in SW, and Pref-1 was not correlated with any bone mineral characteristics in studied groups. Sclerostin was the independent variable that explained 14% of the total variance (R2 × 100) in LS aBMD value only in RG. Adolescent athletes have higher sclerostin compared to UC. Sclerostin was correlated with bone mineral values and predicted areal bone mineral density in RG.

Incidence and predictors of fractures in older adults with and without obesity defined by body mass index versus body fat percentage.

The aim of this study was to determine and compare risk factors associated with incident fractures in older adults with and without obesity, defined by both body mass index (BMI) and body fat percentage. 1,099 older adults (mean±standard deviation age=63.0±7.5) years, participated in this prospective cohort study. Obesity status at baseline was defined by BMI (≥30kg/m2) obtained by anthropometry and body fat percentage (≥30% for men and≥40% for women) assessed by dual-energy X-ray absorptiometry (DXA). Total hip and lumbar spine areal bone mineral density (aBMD) were assessed by DXA up to five years. Incident fractures were self-reported up to 10years. Prevalence of obesity was 28% according to BMI and 43% according to body fat percentage. Obese older adults by BMI, but not body fat percentage, had significantly higher aBMD at the total hip and spine compared with non-obese (both p-value<0.05). Obese older adults by body fat percentage had significantly higher likelihood of all incident fractures (OR: 1.71; CI:1.08, 2.71) and non-vertebral fractures (OR: 1.88; CI:1.16, 3.04) compared with non-obese after adjusting for confounders. Conversely, obese older adults by BMI had a significantly lower likelihood (OR: 0.54; CI:0.31, 0.94) of non-vertebral fractures although this was no longer significant after adjustment for total hip aBMD (all p-value>0.05). Mediation analysis confirmed that aBMD meditated the effects of BMI, but not body fat percentage, on all incident fractures. Higher baseline falls risk score was the only consistent predictor of increased likelihood of incident fracture in obese individuals only, according to both BMI and body fat percentage (both p-value<0.05). Obesity defined by body fat percentage is associated with increased likelihood of incident fractures in community-dwelling older adults, whereas those who are obese according to BMI have reduced likelihood of incident fracture which appears to be explained by higher aBMD. Falls risk assessment may improve identification of obese older adults at increased risk of incident fractures.