Long‐Term Leisure Time Physical Activity and Properties of Bone: A Twin Study

Effects of physical activity on bone properties, when controlled for genetic effects, are not fully understood. We aimed to study the association between long‐term leisure time physical activity (LTPA) and bone properties using twin pairs known to be discordant for leisure time physical activity for at least 30 yr. Volumetric BMD and geometric properties were measured at the tibia shaft and distal end using pQCT in 16 middle‐aged (50–74 yr) same‐sex twin pairs (seven monozygotic [MZ] and nine dizygotic [DZ] pairs) selected from a population‐based cohort. Paired differences between active and inactive co‐twins were studied. Active members of MZ twin pairs had larger cortical bone cross‐sectional area (intrapair difference: 8%, p = 0.006), thicker cortex (12%, p = 0.003), and greater moment of inertia (I_max, 20%, p = 0.024) at the tibia shaft than their inactive co‐twins. At the distal tibia, trabecular BMD (12%, p = 0.050) and compressive strength index (18%, p = 0.038) were also higher in physically active MZ pair members than their inactive co‐twins. The trends were similar, but less consistently so, in DZ pairs as in MZ pairs. Our genetically controlled study design shows that LTPA during adulthood strengthens bones in a site‐specific manner, that is, the long bone shaft has a thicker cortex, and thus higher bending strength, whereas the distal bone has higher trabecular density and compressive strength. These results suggest that LTPA has a potential causal role in decreasing the long‐term risk of osteoporosis and thus preventing osteoporotic fractures.     

Bone mineral accrual in 4‐ to 10‐year‐old precompetitive,recreational gymnasts: A 4‐year longitudinal study

Competitive female gymnasts have greater bone mineral measures than nongymnasts. However, less is known about the effect of recreational and/or precompetitive gymnastics participation on bone development. The purpose of this study was to investigate whether the differences previously reported in the skeleton of competitive female gymnasts are also demonstrated in young children with a current or past participation history in recreational or precompetitive gymnastics. One hundred and sixty‐three children (30 gymnasts, 61 ex‐gymnasts, and 72 nongymnasts) between 4 and 6 years of age were recruited and measured annually for 4 years (not all participants were measured at every occasion). Total‐body (TB), lumbar spine (LS), and femoral neck (FN) bone mineral content (BMC) were measured by dual‐energy X‐ray absorptiometry (DXA). Multilevel random‐effects models were constructed and used to predict differences in TB, LS, and FN BMC between groups while controlling for differences in body size, physical activity, and diet. Gymnasts had 3% more TB and 7% more FN BMC than children participating in other recreational sports at year 4 (p < .05). No differences were found at the LS between groups, and there were no differences between ex‐gymnasts' and nongymnasts' bone parameters (p > .05). These findings suggest that recreational and precompetitive gymnastics participation is associated with greater BMC. This is important because beginner gymnastics skills are attainable by most children and do not require a high level of training. Low‐level gymnastics skills can be implemented easily into school physical education programs, potentially affecting skeletal health. © 2011 American Society for Bone and Mineral Research.     

Bone Mineral Density Is Positively Related to Carotid Intima‐Media Thickness: Findings From a Population‐Based Study in Adolescents and Premenopausal Women

Osteoporosis and cardiovascular disease (CVD) are both common causes of morbidity and mortality. Previous studies, mainly of people older than 60 years, suggest a relationship between these conditions. Our aim was to determine the association between bone characteristics and CVD markers in younger and middle‐aged individuals. Women (n = 3366) and their adolescent offspring (n = 4368) from the UK population‐based cohort study, Avon Longitudinal Study of Parents and Children (ALSPAC), were investigated. We measured total body (TB) and hip bone mineral density (BMD), TB bone area (BA) and bone mineral content (BMC) by dual‐energy X‐ray absorptiometry (DXA), and carotid intima‐media thickness (cIMT) by high‐resolution ultrasound. Arterial distensibility was calculated as the difference between systolic and diastolic arterial diameters. Linear regression determined associations between bone exposures and cIMT (in adolescents) and both cIMT and arterial distensibility (in women), generating partial correlation coefficients. Mean (SD) age of women was 48 (4.2) years, body mass index (BMI) was 26.2 (5.0) kg/m², and 71% were premenopausal. In confounder‐adjusted analyses (age, height, lean mass, fat mass, menopause, smoking, estrogen replacement, calcium/vitamin D supplementation, and education) TB and hip BMD were both positively associated with cIMT (0.071 [0.030, 0.112], p = 0.001; 0.063 [0.025, 0.101], p = 0.001, respectively). Femoral neck BMD and TB BMD, BMC, and BA were positively associated with arterial distensibility. Mean (SD) age of adolescents was 17 (0.4) years, BMI was 23 (4.1) kg/m², and 44.5% were male. Total hip and TB measurements were positively associated with cIMT, with similar magnitudes of association to those found in their mothers. In contrast to most published findings, we identified weak positive associations between BMD and cIMT in predominantly premenopausal women and their adolescent offspring. We found greater femoral neck BMD and TB DXA measurements to be associated with reduced arterial stiffness. Rather than a relationship with preclinical atherosclerosis, in these relatively young populations, we speculate our associations between BMD, cIMT, and arterial distensibility may reflect a shared relationship between bone and vascular growth and development. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.     

Higher premenarcheal bone mass in elite gymnasts is maintained into young adulthood after long‐term retirement from sport: A 14‐year follow‐up

Sports that impact‐load the skeleton during childhood and adolescence increase determinants of bone strength such as bone mineral content and density; however, it is unclear if this benefit is maintained after retirement from the sport. The purpose of this study was to assess whether the previously reported higher bone mass in a group of premenarcheal gymnasts was still apparent 10 years after the cessation of participation and withdrawal of the gymnastics loading stimulus. In 1995, 30 gymnasts 8 to 15 years of age were measured and compared with 30 age‐matched nongymnasts. Twenty‐five former gymnasts and 22 nongymnasts were measured again 14 years later (2009 to 2010). Gymnasts had been retired from gymnastics training and competition for an average of 10 years. Total body (TB), lumbar spine (LS), and femoral neck (FN) bone mineral content (BMC) was assessed at both measurement occasions by dual‐energy X‐ray absorptiometry (DXA). Multivariate analysis of covariance (MANCOVA) was used to compare former gymnasts' and nongymnasts' BMC while controlling for differences in body size and maturation (covariates: age, height, weight, and years from menarche [1995] or age at menarche [2009 to 2010]). Premenarcheal gymnasts (measured in 1995) had significantly greater size‐adjusted TB, LS, and FN BMC (p < 0.05) (15%, 17%, and 12%, respectively) than nongymnasts. Ten years after retirement, gymnasts had maintained similar size‐adjusted TB, LS, and FN BMC differences (p < 0.05) (13%, 19%, and 13%, respectively) when compared with nongymnasts. Bone mass benefits in premenarcheal gymnasts were still apparent even after long‐term (10 years) removal of the gymnastics loading stimulus. © 2012 American Society for Bone and Mineral Research     

Concentric and eccentric isokinetic resistance training similarly increases muscular strength, fat-free soft tissue mass, and specific bone mineral measurements in young women

Summary Women participated in 5 months of unilateral concentric (n = 37) or eccentric (n = 33) isokinetic resistance training of the legs and arms. Limb muscular strength increased as did total body, leg, and arm fat-free soft tissue mass, total body BMC, hip BMD, and forearm BMC and BMD. Isokinetic training benefits bone mineral acquisition. Introduction and hypothesis Isokinetic resistance training (IRT) is osteogenic; however, it is not known if concentric or eccentric modalities of IRT produce differential effects on bone. We tested our hypothesis that high-load eccentric versus concentric mode of IRT would produce greater increases in muscular strength, fat-free soft tissue mass (FFSTM), bone mineral density (BMD) and content (BMC) in trained legs and arms. Methods Participants were randomized to 5 months of concentric (n = 37) or eccentric (n = 33) training. The non-dominant leg and arm were used during training; dominant limbs served as controls. Muscular strength was measured with an isokinetic dynamometer; body composition was measured by dual-energy X-ray absorptiometry. Results Muscular strength of the concentrically and eccentrically trained leg (18.6%; 28.9%) and arm (12.5%; 24.6%) significantly increased with training. Gains in total body (TB) BMC (p < 0.05) and, in the trained limbs, total proximal femur BMD (p < 0.05) and total forearm BMD (p < 0.05) and BMC (p < 0.05) occurred in both groups. FFSTM increased for the TB and trained leg and arm (all p < 0.001) in both modes. Conclusion Regardless of the mode, high-intensity, slow-velocity IRT increases muscular strength and FFSTM of trained limbs and imparts benefits to TB BMC and site-specific BMD and BMC in young women.     

Higher Milk Requirements for Bone Mineral Accrual in Adolescent Girls Bearing Specific Caucasian Genotypes in the VDR Promoter

Low milk intakes hamper bone mineral acquisition during adolescence, especially in European girls. We hypothesized that ethnic‐specific polymorphisms of the vitamin D receptor gene promoter (VDRp) influence this milk/bone association. We evaluated lumbar spine BMC and BMD, milk/dairy products and calcium intakes, markers of P‐Ca metabolism, and VDRp polymorphisms at the Cdx‐2 binding (rs11568820) and ?1012 (rs4516035) loci in 117 healthy European peri‐ and postmenarcheal girls (14.9 ± 1.6 yr) during a 4‐yr follow‐up. Calcium intakes from milk, nonmilk dairy products, and nondairy products averaged 199, 243, and 443 mg/d at the initiation of the study. Results show no association between milk intakes and bone mass accrual in girls bearing an A/A genotype at the ?1012 VDRp locus (30% of the cohort). In contrast, A/G or G/G girls had lower spine BMC (?13%, p = 0.031), BMD (?10%, p = 0.004), and BMD Z‐score (?0.84 SD, p = 0.0003) when their milk intakes were <260 ml/d compared with genotype‐matched girls with higher milk intakes and with girls with an A/A genotype. The negative impact of low milk intake persisted up to 19.0 ± 1.7 yr. These findings suggest that European girls bearing a ?1012 A/G or G/G VDRp genotype should have higher milk/calcium intakes for optimal vertebral mass accrual during adolescence than girls bearing an A/A genotype, a genotype found in 30% of European and 98% of Asian and Sub‐Saharan African populations. VDRp genotype diversity may contribute to the ethnic differences observed in milk requirements for bone health during adolescence.     

Effects of repetitive loading on the growth‐induced changes in bone mass and cortical bone geometry: A 12‐month study in pre/peri‐ and postmenarcheal tennis players

Pre‐ and early puberty may be the most opportune time to strengthen the female skeleton, but there are few longitudinal data to support this claim. Competitive female premenarcheal (pre/peri, n = 13) and postmenarcheal (post, n = 32) tennis players aged 10 to 17 years were followed over 12 months. The osteogenic response to loading was studied by comparing the playing and nonplaying humeri for dual‐energy X‐ray absorptiometry (DXA) bone mineral content (BMC) and magnetic resonance imaging (MRI) total bone area (ToA), medullary area (MedA), cortical area (CoA), and muscle area (MCSA) at the humerus. Over 12 months, growth‐induced gains (nonplaying arm) in BMC, ToA, and CoA were greater in pre/peri (10% to 19%, p < .001) than in post (3% to 5%, p < .05 to .001) players. At baseline, BMC, ToA, CoA, and MCSA were 8% to 18% greater in the playing versus nonplaying arms in pre/peri and post players (all p < .001); MedA was smaller in the playing versus nonplaying arms in post only players (p < .05). When comparing the annual gains in the playing arm relative to changes in the nonplaying arm, the increases in ToA and CoA were greater in pre/peri than post players (all p < .05). The smaller the side‐to‐side differences in BMC and CoA at baseline, the larger the exercise benefits at 12 months (r = ?0.39 to ?0.48, p < .01). The exercise‐induced change in MCSA was predictive of the exercise benefits in BMC in pre/peri players only (p < .05). In conclusion, both pre/peri‐ and postmenarcheal tennis players showed significant exercise‐induced skeletal benefits within a year, with greater benefits in cortical bone geometry in pre/perimenarcheal girls. © 2011 American Society for Bone and Mineral Research.     

Lifestyle Determinants of Bone Mineral: A Comparison Between Prepubertal Asian- and Caucasian-Canadian Boys and Girls

The purpose of this study was to examine the difference in lifestyle and morphometric factors that affect bone mineral and the attainment of peak bone mass in 168 healthy Asian (n = 58) and Caucasian (n = 110) Canadian, prepubertal girls and boys (mean age 8.9 ± 0.7) living in close geographical proximity. DXA (Hologic 4500) scans of the proximal femur (with regions), lumbar spine, and total body (TB) were acquired. We report areal bone mineral densities (aBMD g/cm²) at all sites and estimated volumetric density (νBMD, g/cm³) at the femoral neck. Dietary calcium, physical activity, and maturity were estimated by questionnaire. Of these prepubertal children, all of the boys and 89% of the girls were Tanner stage 1. A 2 × 2 ANOVA demonstrated no difference between ethnicities for height, weight, body fat, or bone mineral free lean mass. Asian children consumed significantly less dietary calcium (35%) on average and were significantly less active (15%) than their Caucasian counterparts (P < 0.001). There were significant ethnicity main effects for femoral neck bone mineral content (BMC) and αBMD (both P < 0.001) and significant sex by ethnicity interactions (P < 0.01). The Asian boys had significantly lower femoral neck BMC (11%), aBMD (8%), and νBMD (4.4%). At the femoral neck, BMFL mass, sex, and physical activity explained 37% of the total variance in aBMD (P < 0.05). In summary, this study demonstrated differences in modifiable lifestyle factors and femoral neck bone mineral between Asian and Caucasian boys. Received: 21 July 1998 / Accepted: 30 September 1999     

Motor Competence in Early Childhood Is Positively Associated With Bone Strength in Late Adolescence

The onset of walking in early childhood results in exposure of the lower limb to substantial forces from weight bearing activity that ultimately contribute to adult bone strength. Relationships between gross motor score (GMS), at 18 months and bone outcomes measured at age 17 years were examined in 2327 participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Higher GMS indicated greater motor competence in weight‐bearing activities. Total hip bone mineral density (BMD) and hip cross‐sectional moment of inertia (CSMI) were assessed from dual‐energy X‐ray absorptiometry (DXA). Bone measures including cortical bone mineral content (BMC), periosteal circumference (PC), cortical thickness (CT), cortical bone area (CBA), cortical BMD (BMD_C) and cross‐sectional moment of inertia (CSMI) were assessed by peripheral quantitative computed tomography (pQCT) at 50% distal‐proximal length. Before adjustment, GMS was associated with hip BMD, CSMI, and tibia BMC, PC, CT, CBA and CSMI (all p < 0.001) but not BMD_C (p > 0.25). Strongest associations (standardized regression coefficients with 95% CI) were between GMS and hip BMD (0.086; 95% CI, 0.067 to 0.105) and tibia BMC (0.105; 95% CI, 0.089 to 0.121). With the exception of hip BMD, larger regression coefficients were observed in males (gender interactions all p < 0.05). Adjustment for lean mass resulted in substantial attenuation of regression coefficients, suggesting associations between impaired motor competence and subsequent bone development are partly mediated by alterations in body composition. In conclusion, impaired motor competence in childhood is associated with lower adolescent bone strength, and may represent a risk factor for subsequent osteoporosis. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).     

Peripheral Bone Mineral Density and Different Intensities of Physical Activity in Children 6–8 Years Old: The Copenhagen School Child Intervention Study

This study aimed to evaluate the association between objectively measured habitual physical activity and calcaneal and forearm bone mineral density (BMD, g/cm²), one mechanically more loaded and one less loaded skeletal region, in children aged 6–8 years. BMD was measured in 297 boys and 265 girls by peripheral dual-energy X-ray absorptiometry in the forearm and calcaneus. An accelerometer registered the level of physical activity during 4 days (2 weekdays and the weekend). Weight, height, and skinfold thickness were measured. In order to establish thresholds (count · min⁻¹) for bone-stimulating physical activity, we evaluated different definitions of vigorous physical activity. The boys had 3.2% higher distal forearm bone mineral content (BMC, P < 0.001) and 4.5% higher distal forearm BMD (P < 0.001) than the girls. They also carried out 9.7% more daily physical activity and spent 14.6–19.0% more time in vigorous physical activity (all P < 0.05) compared to the girls. In contrast, the girls had 3.8% higher calcaneal BMC (P < 0.01) and 2.5% higher calcaneal BMD (P < 0.05) than the boys. Both calcaneal and forearm BMD were significantly related to total time of daily physical activity as well as with intense physical activity above all the chosen cut-off points (all P < 0.05). The β value for mean count · min⁻¹ physical activity was significantly lower than that for all the chosen cut-off points of vigorous activity both for calcaneal and distal forearm BMD. This study suggests that both habitual daily physical activity and amount of vigorous physical activity in children aged 6–8 years are associated with appendicular BMD.     

Deleterious Effects of Glucocorticoid Replacement on Bone in Women After Long‐Term Remission of Cushing's Syndrome

Endogenous hypercortisolism and high‐dose and long‐term glucocorticoid (GC) therapy reduce bone mass. Patients in remission after successful treatment of Cushing's syndrome (CS) often present hypoadrenalism and require long‐term GC replacement. The aim of our study was to evaluate whether this GC “replacement” had any further effect on bone in women after long‐term remission of CS. Thirty‐seven women (mean age: 50 ± 14 yr; 27 of pituitary and 10 of adrenal origin) with cured CS (mean time of cure: 11 ± 6 yr), 14 with active CS, and 85 sex‐, body mass index (BMI)‐, and age‐matched controls were enrolled. BMD and BMC were measured by DXA scanning. Bone biochemical markers were also measured. Duration and dose of GC replacement and duration of endogenous hypercortisolism were calculated. Cured and active CS patients had less BMC, BMD, and osteocalcin than controls (p < 0.01). These differences were observed in estrogen‐sufficient women but not in those with estrogen deficiency. Duration of GC treatment (mean: 42 mo; range, 2–420 mo) and endogenous hypercortisolism (mean: 70 mo; range, 13–241 mo) negatively correlated with BMC and lumbar spine BMD. After regression analysis, the main predictor of abnormal BMC and BMD was the duration of GC replacement (p < 0.01). Patients treated for CS persistently have less bone mass despite long‐term cure. Both duration of endogenous hypercortisolism and mainly exogenous “replacement” therapy with GC negatively affect bone mass. Thus, the additional deleterious effect of GC for the treatment of adrenal axis suppression should be considered.     

Physical Activity Benefits the Skeleton of Children Genetically Predisposed to Lower Bone Density in Adulthood

Both genetics and physical activity (PA) contribute to bone mineral density (BMD), but it is unknown if the benefits of physical activity on childhood bone accretion depend on genetic risk. We, therefore, aimed to determine if PA influenced the effect of bone fragility genetic variants on BMD in childhood. Our sample comprised US children of European ancestry enrolled in the Bone Mineral Density in Childhood Study (N = 918, aged 5 to 19 years, and 52.4% female). We used a questionnaire to estimate hours per day spent in total, high‐, and low‐impact PA. We calculated a BMD genetic score (% BMD lowering alleles) using adult genome‐wide association study (GWAS)‐implicated BMD variants. We used dual‐energy X‐ray absorptiometry to estimate femoral neck, total hip, and spine areal‐BMD and total body less head (TBLH) bone mineral content (BMC) Z‐scores. The BMD genetic score was negatively associated with each bone Z‐score (eg, TBLH‐BMC: estimate = –0.03, p = 1.3 × 10^?6). Total PA was positively associated with bone Z‐scores; these associations were driven by time spent in high‐impact PA (eg, TBLH‐BMC: estimate = 0.05, p = 4.0 × 10^?10) and were observed even for children with lower than average bone Z‐scores. We found no evidence of PA‐adult genetic score interactions (p interaction > 0.05) at any skeletal site, and there was no evidence of PA‐genetic score–Tanner stage interactions at any skeletal site (p interaction > 0.05). However, exploratory analyses at the individual variant level revealed that PA statistically interacted with rs2887571 (ERC1/WNT5B) to influence TBLH‐BMC in males (p interaction = 7.1 × 10^?5), where PA was associated with higher TBLH‐BMC Z‐score among the BMD‐lowering allele carriers (rs2887571 AA homozygotes: estimate = 0.08 [95% CI 0.06, 0.11], p = 2.7 × 10^?9). In conclusion, the beneficial effect of PA on bone, especially high‐impact PA, applies to the average child and those genetically predisposed to lower adult BMD (based on GWAS‐implicated BMD variants). Independent replication of our exploratory individual variant findings is warranted. © 2016 American Society for Bone and Mineral Research.     

Influence of a 3‐year exercise intervention program on fracture risk,bone mass,and bone size in prepubertal children

Published prospective pediatric exercise intervention studies are short term and use skeletal traits as surrogate endpoints for fractures, whereas other reports infer exercise to be associated with more trauma and fractures. This prospective, controlled exercise intervention study therefore followed both skeletal traits and fracture risk for 36 months. Fractures were registered in children aged 7 to 9 years; there were 446 boys and 362 girls in the intervention group (2129 person‐years) and 807 boys and 780 girls in the control group (4430 person‐years). The intervention included school physical education of 40 minutes per day for 3 years. The control children achieved the Swedish standard of 60 minutes per week. In a subsample of 76 boys and 48 girls in the intervention group and 55 boys and 44 girls in the control group, bone mineral content (BMC, g) and bone width (cm) were followed in the lumbar spine and hip by dual‐energy X‐ray absorptiometry (DXA). The rate ratio (RR) for fractures was 1.08 (0.71, 1.62) [mean (95% confidence interval)]. In the DXA‐measured children, there were no group differences at baseline in age, anthropometrics, or bone traits. The mean annual gain in the intervention group in lumbar spine BMC was 0.9 SD higher in girls and 0.8 SD higher in boys (both p < .001) and in third lumbar vertebra width 0.4 SD higher in girls and 0.3 SD higher in boys (both p < .05) than in control children. It is concluded that a moderately intense 3‐year exercise program in 7‐ to 9‐year‐old children increases bone mass and possibly also bone size without increasing fracture risk. © 2011 American Society for Bone and Mineral Research     

Eight Months of Regular In‐School Jumping Improves Indices of Bone Strength in Adolescent Boys and Girls: The POWER PE Study

The POWER PE study was an 8‐mo, randomized, controlled, school‐based exercise intervention designed to apply known principles of effective bone loading to practical opportunities to improve life‐long musculoskeletal outcomes. A total of 99 adolescents (46 boys and 53 girls) with a mean age of 13.8 ± 0.4 yr (peri‐ to postpubertal) volunteered to participate. Intervention subjects performed 10 min of jumping activity in place of regular physical education (PE) warm up. Control subjects performed usual PE warm‐up activities. Bone mass (DXA and QUS) was assessed at baseline and follow‐up along with anthropometry, maturity, muscle power, and estimates of physical activity and dietary calcium. Geometric properties (such as femoral neck [FN] moment of inertia) were calculated from DXA measures. Boys in the intervention group experienced improvements in calcaneal broadband ultrasound attenuation (BUA) (+5.0%) and fat mass (?10.5%), whereas controls did not (+1.4% and –0.8%, respectively). Girls in the intervention group improved FN BMC (+13.9%) and lumbar spine (LS) BMAD (+5.2%) more than controls (+4.9% and +1.5%, respectively). Between‐group comparisons of change showed intervention effects only for whole body (WB) BMC (+10.6% versus +6.3%) for boys. Boys in the intervention group gained more lean tissue mass, trochanter (TR) BMC, LS BMC, and WB BMC and lost more fat mass than girls in the intervention group (p < 0.05). Ten minutes of jumping activity twice a week for 8 mo during adolescence seems to improve bone accrual in a sex‐specific manner. Boys increased WB bone mass and BUA, and reduced fat mass, whereas girls improved bone mass at the hip and spine.     

Effect of Surgery Versus Observation: Skeletal 5‐Year Outcomes in a Randomized Trial of Patients With Primary HPT (the SIPH Study)

Mild primary hyperparathyroidism (PHPT) is known to affect the skeleton, even though patients usually are asymptomatic. Treatment strategies have been widely discussed. However, long‐term randomized studies comparing parathyroidectomy to observation are lacking. The objective was to study the effect of parathyroidectomy (PTX) compared with observation (OBS) on bone mineral density (BMD) in g/cm² and T‐scores and on biochemical markers of bone turnover (P1NP and CTX‐1) in a prospective randomized controlled study of patients with mild PHPT after 5 years of follow‐up. Of 191 patients with mild PHPT randomized to either PTX or OBS, 145 patients remained for analysis after 5 years (110 with validated DXA scans). A significant decrease in P1NP (p < 0.001) and CTX‐1 (p < 0.001) was found in the PTX group only. A significant positive treatment effect of surgery compared with observation on BMD (g/cm²) was found for the lumbar spine (LS) (p = 0.011), the femoral neck (FN) (p < 0.001), the ultradistal radius (UDR) (p = 0.042), and for the total body (TB) (p < 0.001) but not for the radius 33% (Rad33), where BMD decreased significantly also in the PTX group (p = 0.012). However, compared with baseline values, there was no significant BMD increase in the PTX group, except for the lumbar spine. In the OBS group, there was a significant decrease in BMD (g/cm²) for all compartments (FN, p < 0.001; Rad33, p = 0.001; UDR, p = 0.006; TB, p < 0.001) with the exception of the LS, where BMD was stable. In conclusion, parathyroidectomy improves BMD and observation leads to a small but statistically significant decrease in BMD after 5 years. Thus, bone health appears to be a clinical concern with long‐term observation in patients with mild PHPT. © 2017 American Society for Bone and Mineral Research.     

A comparison of parathyroid hormone‐related protein (1‐36) and parathyroid hormone (1‐34) on markers of bone turnover and bone density in postmenopausal women: The PrOP study

Parathyroid hormone‐related protein (PTHrP)(1‐36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but it has not been directly compared with parathyroid hormone (PTH)(1‐34). We performed a 3‐month randomized, prospective study in 105 postmenopausal women with low bone density or osteoporosis, comparing daily subcutaneous injections of PTHrP(1‐36) to PTH(1‐34). Thirty‐five women were randomized to each of three groups: PTHrP(1‐36) 400 µg/day; PTHrP(1‐36) 600 µg/day; and PTH(1‐34) 20 µg/day. The primary outcome measures were changes in amino‐terminal telopeptides of procollagen 1 (PINP) and carboxy‐terminal telopeptides of collagen 1 (CTX). Secondary measures included safety parameters, 1,25(OH)₂ vitamin D, and BMD. The increase in bone resorption (CTX) by PTH(1‐34) (92%) (p < 0.005) was greater than for PTHrP(1‐36) (30%) (p < 0.05). PTH(1‐34) also increased bone formation (PINP) (171%) (p < 0.0005) more than either dose of PTHrP(1‐36) (46% and 87%). The increase in PINP was earlier (day 15) and greater than the increase in CTX for all three groups. LS BMD increased equivalently in each group (p < 0.05 for all). Total hip (TH) and femoral neck (FN) BMD increased equivalently in each group but were only significant for the two doses of PTHrP(1‐36) (p < 0.05) at the TH and for PTHrP(1‐36) 400 (p < 0.05) at the FN. PTHrP(1‐36) 400 induced mild, transient (day 15) hypercalcemia. PTHrP(1‐36) 600 required a dose reduction for hypercalcemia in three subjects. PTH(1‐34) was not associated with hypercalcemia. Each peptide induced a marked biphasic increase in 1,25(OH)₂D. Adverse events (AE) were similar among the three groups. This study demonstrates that PTHrP(1‐36) and PTH(1‐34) cause similar increases in LS BMD. PTHrP(1‐36) also increased hip BMD. PTH(1‐34) induced greater changes in bone turnover than PTHrP(1‐36). PTHrP(1‐36) was associated with mild transient hypercalcemia. Longer‐term studies using lower doses of PTHrP(1‐36) are needed to define both the optimal dose and full clinical benefits of PTHrP. © 2013 American Society for Bone and Mineral Research. © 2013 American Society for Bone and Mineral Research.     

A comparison of bone quality at the distal radius between Asian and white adolescents and young adults: An HR‐pQCT study

Paradoxically, Asians have lower areal bone mineral density (aBMD), but their rates of hip and wrist fractures are lower than whites. Therefore, we used high‐resolution pQCT (HR‐pQCT) to determine whether differences in bone macrostructure and microstructure, BMD, and bone strength at the distal radius were apparent in Asian (n = 91, 53 males, 38 females, [mean ± SD] 17.3 ± 1.5 years) and white (n = 89, 46 males, 43 females, 18.1 ± 1.8 years) adolescents and young adults. HR‐pQCT outcomes included total BMD (Tt.BMD), trabecular bone volume fraction (BV/TV), and trabecular number (Tb.N), thickness (Tb.Th), and separation (Tb.Sp). We used an automated segmentation algorithm to determine total bone area (Tt.Ar), and cortical BMD (Ct.BMD), porosity (Ct.Po), and thickness (Ct.Th), and we applied finite element (FE) analysis to HR‐pQCT scans to estimate bone strength. We fit sex‐specific multivariable regression models to compare bone outcomes between Asians and whites, adjusting for age, age at menarche (girls), lean mass, ulnar length, dietary calcium intake, and physical activity. In males, after adjusting for covariates, Asians had 11% greater Tt.BMD, 8% greater Ct.BMD, and 25% lower Ct.Po than whites (p < 0.05). Also, Asians had 9% smaller Tt.Ar and 27% greater Ct.Th (p < 0.01). In females, Asians had smaller Tt.Ar than whites (16%, p < 0.001), but this difference was not significant after adjusting for covariates. Asian females had 5% greater Ct.BMD, 12% greater Ct.Th, and 11% lower Tb.Sp than whites after adjusting for covariates (p < 0.05). Estimated bone strength did not differ between Asian and white males or females. Our study supports the notion of compensatory elements of bone structure that sustain bone strength; smaller bones as observed between those of Asian origin compared with white origin have, on average, more dense, less porous, and thicker cortices. Longitudinal studies are needed to determine whether ethnic differences in bone structure exist in childhood, persist into old age, and whether they influence fracture risk.     

Weight-bearing bones are more sensitive to physical exercise in boys than in girls during pre- and early puberty: a cross-sectional study

Summary  We carried out a cross-section study of the sex-specific relationship between bone mineral content and physical activity at sites with different loading in pre- and early pubertal girls and boys. There was significant sensitivity of bone mineral content of the hip to physical exercise in boys, but not in girls. Background  Since little is known whether there are sex differences in sensitivity of bone to loading, we investigated sex differences in the cross-sectional association between measures of physical activity (PA) and bone mass and size in pre- and early pubertal children of both sexes. Methods  We measured bone mineral content/density (BMC/BMD) and fat-free mass (FFM) in 269 6- to 13-year-old children from randomly selected schools by dual-energy X-ray absorptiometry. Physical activity (PA) was measured by accelerometers and lower extremity strength by a jump-and-reach test. Results  Boys (n = 128) had higher hip and total body BMC and BMD, higher FFM, higher muscle strength and were more physically active than girls (n = 141). Total hip BMC was positively associated with time spent in total and vigorous PA in boys (r = 0.20–0.33, p < 0.01), but not in girls (r = 0.02–0.04, p = ns), even after adjusting for FFM and strength. While boys and girls in the lowest tertile of vigorous PA (22 min/day) did not differ in hip BMC (15.62 vs 15.52 g), boys in the highest tertile (72 min/day) had significantly higher values than the corresponding girls (16.84 vs 15.71 g, p < 0.05). Conclusions  Sex differences in BMC during pre- and early puberty may be related to a different sensitivity of bone to physical loading, irrespective of muscle mass.     

Ethnic and Gender Differences in Bone Mineral Density and Bone Turnover in Young Adults: Effect of Bone Size

Generally, the incidence of osteoporotic fracture is lower in black populations and in men. These effects of ethnicity and gender may result from differences in peak bone mineral density (PBMD) and bone turnover (BT), which in turn are affected by bone size. Therefore, the aims of this study were to examine the effects of ethnicity and gender on bone mineral density (BMD) and BT in young African-Caribbean and Caucasian adults, and to adjust for the effect of bone size on BMD and BT. BMD was measured at the lumbar spine, L2–L4 (LS), total body (TB) and femoral neck (FN) by dual-energy X-ray absorptiometry in 44 blacks (16 men, 28 women) and 59 whites (28 men, 31 women) ages 20–37 years. We measured serum bone-specific alkaline phosphatase (BAP) and serum osteocalcin (OC) as markers of bone formation and urinary immunoreactive free deoxypyridinoline (ifDpd) and crosslinked N-telopeptide of type I collagen (NTx) as markers of bone resorption. To adjust the data for any differences in bone size, we calculated: (a) bone mineral apparent density (BMAD), an estimated volumetric bone density which attempts to normalize BMD measurements for bone size; and (b) bone resorption markers as a ratio to total body bone mineral content (TB BMC). Two-way analysis of variance was used to compare the effects of race and gender, and to test for any interaction between these two factors. Blacks had higher BMD compared with whites at the TB (p<0.001), LS (p= 0.0001) and FN (p= 0.0005). This increase remained significant at the LS only after calculating BMAD. Men had higher BMD at all sites (except at the LS). This increase was no longer significant at the FN after calculating BMAD, and LS BMAD was actually greater in women (p<0.0001). Blacks and whites had similar concentrations of turnover markers, but men had higher bone turnover markers than women (BAP, p<0.0001; OC, p= 0.002; ifDpd, p= 0.03; NTx, p<0.0001). This increase in bone resorption markers was no longer significant after adjusting for TB BMC (except for NTx in whites). We conclude that the skeletal advantage in blacks during young adulthood is not explained by bone size. However, it seems probable that bone size effects partially explain gender differences in BMD and bone turnover. Received: 2 February 1999 / Accepted: 2 December 1999     

Contribution of the Vertebral Posterior Elements in Anterior–Posterior DXA Spine Scans in Young Subjects

Because DXA is a projection technique, anterior–posterior (AP) measurements of the spine include the posterior elements and the vertebral body. This may be a disadvantage because the posterior elements likely contribute little to vertebral fracture resistance. This study used QCT to quantify the impact of the posterior elements in DXA AP spine measures. We examined 574 subjects (294 females and 280 males), age 6–25 yr, with DXA and QCT. QCT measures were calculated for the cancellous bone region and for the vertebral body including and excluding the posterior elements. DXA data were analyzed for the entire L₃ vertebra and for a 10‐mm slice corresponding to the QCT scan region. BMC and BMD were determined and compared using Pearson's correlation. The posterior elements accounted for 51.4 ± 4.2% of the total BMC, with a significant difference between males (49.9 ± 4.0%) and females (52.8 ± 3.9%, p < 0.001). This percentage increased with age in younger subjects of both sexes (p < 0.001) but was relatively consistent after age 17 for males and 16 for females (p > 0.10). DXA areal BMD and QCT volumetric BMD correlated strongly for the whole vertebra including the posterior elements (R = 0.83), with BMC measures showing a stronger relationship (R = 0.93). Relationships were weaker when excluding the posterior elements. We conclude that DXA BMC provides a measure of bone that is most consistent with QCT and that the contribution of the posterior elements is consistent in young subjects after sexual maturity.