Lumbar Spine Areal Bone Mineral 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.

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.

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 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.

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.

Effect of Testosterone Treatment for Delayed Puberty in Duchenne Muscular Dystrophy

Objective: To evaluate the impact of pubertal induction with testosterone on bone health, body composition, and motor function in boys with Duchenne muscular dystrophy (DMD) receiving long-term glucocorticoid. Study Design: A retrospective, observational, pre-post study investigating the impact of testosterone therapy on bone mass accrual, vertebral fracture incidence, body composition, motor function, and quality of life in boys with DMD. All those boys aged ≥14 years, on chronic steroid therapy, who had delayed puberty, and were receiving oral testosterone or oral and then transitioned to intramuscular testosterone, to complete virilization, were included. Prior/concomitant zoledronic acid use was included. The primary outcome was lumbar spine areal bone mineral density (BMD LS). Results: Puberty was induced, using oral testosterone undecanoate in 16 individuals, 10 of whom had transited to intramuscular testosterone at time of assessment. Median age at testosterone onset was 14.5 years (range 14–17.7). Median duration of testosterone therapy was 2.5 years (range 1.0–4.5). There was statistically significant increase in median BMD LS (0.523–0.700, p < 0.001) and median annualized percentage change of BMD LS (–1.34 to +10.08%, p < 0.001), with median Tanner stage 4 at evaluation (range 2–4). Ten of 14 assessed had no progression in vertebral fractures. Fat mass index (FMI) standard deviation score (SDS), lean body mass index (LBMI) SDS, and percentage change of FMI and LBMI were statistically unchanged. Cardiac function remained stable. Motor function in non-ambulatory individuals with Egen Klassifikation scores improved in 7 of 8. Conclusion: Testosterone for delayed puberty acted as an adjunct to bisphosphonates to increase bone density and stabilize vertebral fracture in most boys with DMD.

Bone densities and bone geometry in children and adolescents with arthrogryposis.

To describe bone densitometry results using lumbar spine dual-energy X-ray absorptiometry and forearm peripheral quantitative computed tomography (pQCT) in children with arthrogryposis multiplex congenita (AMC). Prospective study. Lumbar spine areal bone mineral density (BMD) was measured in 58 participants (mean age 6.8years, range 1month to 19.7years; 26 males). The diagnostic subgroup was Amyoplasia in 27 participants, distal arthrogryposis (unclassified, n=13; type 2A, n=1; type 2B, n=2; type 8, n=2) in 18 patients, an unclassified form of arthrogryposis in 6 patients, and a syndromic form of arthrogryposis in 7 patients. The mean lumbar spine areal BMD was -0.4 (SD: 1.5) which was significantly below 0 (p<0.05, one-sample t-test). The mean lumbar spine bone mineral apparent density z-score (+0.4 [SD: 1.4]), a measure that is largely independent of bone size, was not significantly different from 0 (P>0.05). A subset of 22 patients aged 6years or older (mean age 10.9years, 11 males) had forearm pQCT analysis. Mean z-scores for trabecular and cortical volumetric BMD at the radius were similar to healthy controls. Radius periosteal bone circumference and bone mineral content were appropriate for height. These densitometric results did not differ between patients with Amyoplasia or individuals with other diagnoses. Low areal BMD in children and adolescents with AMC reflects their smaller bone size rather than a specific bone mass deficit. These data do not suggest that children and adolescents with AMC in general require regular monitoring by bone densitometry unless there are specific clinical concerns.

Musculoskeletal phenotype in two unrelated individuals with a recurrent nonsense variant in SGMS2

Heterozygous mutations in the gene encoding the sphingomyelin synthase 2, SGMS2, have recently been linked to childhood-onset osteoporosis and skeletal dysplasia. One nonsense variant at position c.148C>T (p.Arg50*) has been associated with mild bone fragility with or without cranial sclerosis. Here we assessed the effect of the SGMS2 p.Arg50* variant in two unrelated probands with childhood-onset osteoporosis and their unaffected family members. We found that the p.Arg50* variant was associated with phenotypic variability, ranging from absence of a bone phenotype to severe vertebral compression fractures and low lumbar spine areal bone mineral density (BMD) as measured by dual energy x-ray absorptiometry. Peripheral quantitative computed tomography of the radius and tibia in the two probands revealed low cortical volumetric BMD and reduced cortical thickness. In addition, both probands were obese and suffered from muscle function deficits compared to sex- and age-matched controls. Long-term bisphosphonate treatment was associated with reshaping of previously compressed vertebral bodies.

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.

A Multicenter Observational Cohort Study to Evaluate the Effects of Bisphosphonate Exposure on Bone Mineral Density and Other Health Outcomes in Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is characterized by low bone mass and bone fragility. Using data from a large cohort of individuals with OI from the Osteogenesis Imperfecta Foundation's linked clinical research centers, we examined the association between exposure to bisphosphonate (BPN) treatment (past or present) and lumbar spine (LS) areal bone mineral density (aBMD), fractures, scoliosis, and mobility. From 466 individuals, we obtained 1394 participant‐age LS aBMD data points. Though all OI subtypes were examined, primary analyses were restricted to type I OI (OI‐1). Using linear regression, we constructed expected OI‐1 LS aBMD‐for‐age curves from the data from individuals who had never received BPN. LS aBMD in those who had been exposed to BPN was then compared with the computed expected aBMD. BPN exposure in preadolescent years (age <14 years) was associated with a LS aBMD that was 9% more than the expected computed values in BPN‐naïve individuals (p < 0.01); however, such association was not observed across all ages. Exposure to i.v. BPN and treatment duration >2 years correlated with LS aBMD in preadolescent individuals. BPN exposure also had a significant association with non‐aBMD clinical outcome variables. Logistic regression modeling predicted that with BPN exposure, a 1‐year increase in age would be associated with an 8.2% decrease in fracture probability for preadolescent individuals with OI‐1, compared with no decrease in individuals who had never received any BPN (p < 0.05). In preadolescent individuals with OI‐1, a 0.1 g/cm2 increase in LS aBMD was associated with a 10.6% decrease in scoliosis probability, compared with a 46.8% increase in the BPN‐naïve group (p < 0.01). For the same changes in age and LS aBMD in preadolescent individuals, BPN exposure was also associated with higher mobility scores (p < 0.01), demonstrating that BPN treatment may be associated with daily function. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Effect of Exercise Modality During Weight Loss on Bone Health in Older Adults With Obesity and Cardiovascular Disease or Metabolic Syndrome: A Randomized Controlled Trial.

The objective of this study was to determine the ability of either aerobic or resistance training to counter weight-loss-associated bone loss in older adults. There were 187 older adults (67 years, 70% women, 64% white) with obesity (BMI = 34.5 ± 3.7 kg/m2 ) and cardiovascular disease and/or metabolic syndrome who were randomized to participate in an 18-month, community-based trial, with a follow-up assessment at 30 months. Intervention arms included: weight loss alone (WL; 7% to 10% baseline weight), WL plus aerobic training (WL + AT), and WL plus resistance training (WL + RT), as well as DXA-acquired total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD), and trabecular bone score (TBS). Biomarkers of bone turnover (procollagen type 1 N-terminal propeptide, C-terminal telopeptide of type 1 collagen) were measured at baseline, 6, 18, and 30 (aBMD and TBS only) months. CT-acquired hip and spine volumetric BMD (vBMD), cortical thickness, and bone strength were measured in a subset at baseline (n = 55) and 18 months. Total hip aBMD was reduced by 2% in all groups at 18 months, with a primary analysis showing no significant treatment effects for any DXA, biomarker, or CT outcome. After adjustment for WL and follow-up at 30 months, secondary analyses revealed that total hip [-0.018 (-0.023 to -0.012) g/cm2 versus -0.025 (-0.031 to -0.019) g/cm2 ; p = 0.05] and femoral neck [-0.01 (-0.009 to 0.008) g/cm2 versus -0.011 (-0.020 to -0.002) g/cm2 ; p = 0.06] aBMD estimates were modestly attenuated in the WL + RT group compared with the WL group. Additionally, lumbar spine aBMD was increased in the WL [0.015 (0.007 to 0.024) g/cm2 ] and the WL + RT [0.009 (0.000 to 0.017) g/cm2 ] groups compared with the WL + AT [-0.003 (-0.012 to 0.005)g/cm2 ] group; both p ≤ 0.01. Community-based exercise does not prevent bone loss during active WL in older adults; however, adding RT may help minimize long-term hip bone loss. © 2018 American Society for Bone and Mineral Research.