Influence of physical activity and skeleton geometry on bone mass at the proximal femur in 10- to 12-year-old children—a longitudinal study

Summary

Physical activity (PA) have long been identified as a determining factor of the mineralization of the skeleton, particularly in children. Our research supports the hypothesis that the geometry of the pelvis and proximal femur (PF) might moderate the effect of PA in the relative mineralization of the PF subregions.

Introduction

Using a longitudinal observational study with two evaluations and a 1-year follow-up interval, we investigated the influence of PA and skeletal geometry in bone mineral density (BMD) and bone mass distribution at the PF in 96 girls and 81 boys (10–12 years). It is plausible that the geometry of the pelvis-PF structure moderates mechanical forces exerted at the hip and therefore creates different degrees of mineralization among PF subregions.

Methods

Whole body and left hip dual X-ray absorptiometry scans were used to derive geometric measures of the pelvis—inter-acetabular distance (IAD) and PF abductor lever arm (ALA). BMD was measured at the integral, superolateral (SL), and inferomedial (IM) femoral neck (FN), and at the trochanter (TR). These subregions were used to represent bone mass distribution via three BMD ratios: FN/PF, IM/SL, and TR/PF. PA was measured using accelerometry and a bone-specific PA questionnaire (BPAQ).

Results

A longitudinal data approach revealed BPAQ as a positive predictor for all BMD variables (p?<?0.05) except TR BMD in girls and FN BMD in boys. Comparing the most active with the less-active participants, the greatest benefits of PA were observed at the FN of the girls with the lowest IAD (p?<?0.001), at the FN of the boys with the highest IAD (p?<?0.001) and at the TR of the boys with the lowest ALA (p?<?0.01).

Conclusions

Geometric measures of IAD and ALA seem to moderate the effect of PA role in the relative mineralization of the PF regions. On the other hand, absolute BMD levels appear to be determined by mechanical loading.     

SHBG levels are associated with bone loss and vertebral fractures in patients with prostate cancer

Summary

Fractures are increased among prostate cancer patients. No data have been reported in patients with prostate cancer about the relation between serum sex hormone-binding globulin (SHBG) and bone metabolism. We found that SHBG levels were inversely related to bone mass and vertebral fractures in this population.

Introduction

Fractures are increased among prostate cancer patients, especially those on androgen deprivation therapy (ADT), but few data are available on the role of SHBG in their bone status. Our objective was to analyze the relation between serum SHBG and bone metabolism in prostate cancer patients.

Methods

This is a cross-sectional study including 91 subjects with prostate cancer (54 % with ADT). We measured serum levels of SHBG and sex steroids, bone mineral density (BMD) by dual-energy X-ray absorptiometry, and prevalent radiographic vertebral fractures.

Results

SHBG levels were inversely related to BMD (femoral neck: r?=??0.299, p?=?0.00; total hip: r?=??0.259, p?=?0.019). Subjects with osteoporosis had higher SHBG concentrations than patients without osteoporosis (60.97?±?39.56 vs 44.45?±?23.32 nmol/l, p?=?0.022). Patients with SHBG levels in the first quartile (>57.6 nmol/l) had an odds ratio (OR) for osteoporosis of 2.59 (95 % CI, 1.30–5.12; p?=?0.009) compared with patients with lower SHBG levels. In patients with SHBG >57.6 nmol/l, the OR for vertebral fractures was 2.34 (95 % CI, 1.15–4.78; p?=?0.034). The calculated OR was higher after adjustment for age (OR, 5.16; 95 % CI, 1.09–24.49; p?=?0.039), estrogens (OR, 6.45; 95 % CI, 1.44–28.95; p?=?0.023), and androgens (OR, 5.51; 95 % CI, 1.36–22.37; p?=?0.017).

Conclusions

In prostate cancer patients, SHBG levels were inversely related to bone mass and vertebral fractures. Determination of the serum SHBG level may constitute a useful and straightforward marker for predicting the severity of osteoporosis in these patients.     

Skeletal health in adult patients with classic galactosemia

Summary

This study evaluated bone health in adults with galactosemia. Associations between bone mineral density (BMD) and nutritional and biochemical variables were explored. Calcium level predicted hip and spine BMD, and gonadotropin levels were inversely associated with spinal BMD in women. These results afford insights into management strategies for these patients.

Introduction

Bone loss is a complication of galactosemia. Dietary restriction, primary ovarian insufficiency in women, and disease-related alterations of bone metabolism may contribute. This study examined relationships between clinical factors and BMD in patients with galactosemia.

Methods

This cross-sectional sample included 33 adults (16 women) with classic galactosemia, mean age 32.0?±?11.8 years. BMD was measured by dual-energy X-ray absorptiometry, and was correlated with age, height, weight, fractures, nutritional factors, hormonal status, and bone biomarkers.

Results

There was a significant difference in hip BMD between women and men (0.799 vs. 0.896 g/cm², p?=?0.014). The percentage of subjects with BMD-Z <?2.0 was also greater for women than men [33 vs. 18 % (spine), 27 vs. 6 % (hip)], and more women reported sustaining fractures. Bivariate analyses yielded correlations between BMI and BMD-Z [at the hip in women (r?=?0.58, p?<?0.05) and spine in men (r?=?0.53, p?<?0.05)]. In women, weight was also correlated with BMD-Z (r?=?0.57, p?<?0.05 at hip), and C-telopeptides (r?=??0.59 at spine and ?0.63 hip, p?<?0.05) and osteocalcin (r?=??0.71 at spine and ?0.72 hip, p?<?0.05) were inversely correlated with BMD-Z. In final regression models, higher gonadotropin levels were associated with lower spinal BMD in women (p?=?0.017); serum calcium was a significant predictor of hip (p?=?0.014) and spine (p?=?0.013) BMD in both sexes.

Conclusions

Bone density in adults with galactosemia is low, indicating the potential for increased fracture risk, the etiology of which appears to be multifactorial.     

Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months

Summary

In vitro data suggest that myokine irisin may affect bone metabolism by promoting osteoblast differentiation while inhibiting osteoclast differentiation. In this study, circulating irisin levels were associated with previous osteoporotic fractures but not with bone mass and were not affected by denosumab or teriparatide treatment for 3 months.

Introduction

This study aimed to evaluate predictors of circulating irisin in postmenopausal women with low bone mass and to assess a potential effect of denosumab or teriparatide treatment for 3 months.

Methods

Serum samples for irisin measurement were obtained from (a) postmenopausal women with low bone mass (lumbar spinal [LS] or femoral neck [FN] bone mineral density [BMD] T-score ≤?2.0) and their age-matched controls at baseline and 3 months after denosumab (Dmab) injection (Dmab group, n?=?50; Dmab control group, n?=?25) and (b) women with more severe disease (LS or FN BMD T-score ≤?2.8) and their age-matched controls at the above-mentioned time points after teriparatide (TPTD) initiation (TPTD group, n?=?25; TPTD control group, n?=?25).

Results

At baseline, irisin levels were inversely correlated with age (partial coefficient (r _p )?=??0.24; p?=?0.009), parathyroid hormone (PTH) (r _p ?=??0.30; p?=?0.001), and creatinine (r _p ?=??0.23; p?=?0.016) in univariate analysis, and were lower in women with (n?=?26; 41.6?±?2.7 ng/dL) than without previous osteoporotic fracture(s) (n?=?99; 51.0?±?1.6 ng/dL; p?=?0.007). In multiple linear regression, previous osteoporotic fracture(s) and PTH were independently negatively associated with irisin [p?=?0.04, CI ?16.1 to ?0.4 and p?=?0.002, CI ?0.3 to ?0.07, respectively], but only the association with PTH remained after controlling for creatinine levels. Serum irisin levels were not different between women with or without low bone mass and were not affected by either Dmab or TPTD treatment for 3 months.

Conclusions

Circulating irisin levels were associated with previous osteoporotic fracture(s); whether this association is independent or is due to confounding by lower muscle mass, potentially reflected by lower creatinine levels, remains to be fully clarified.     

Cold-activated brown adipose tissue is an independent predictor of higher bone mineral density in women

Summary

In animals, defective brown adipogenesis leads to bone loss. Whether brown adipose tissue (BAT) mass relates to bone mineral density (BMD) in humans is unclear. We determined the relationship between BAT mass and BMD by cold-stimulated positron-emission tomography (PET) and dual-energy X-ray absorptiometry (DXA) in healthy volunteers. Higher BAT mass was associated with higher BMD in healthy women, but not in men, independent of age and body composition.

Introduction

Contrary to the traditional belief that BAT is present only in infants, recent studies revealed significant depots of BAT present in adult humans. In animals, defective brown adipogenesis leads to bone loss. While white adipose tissue mass is a known determinant of BMD in humans, the relationship between BAT and BMD in humans is unclear. We thus examined the relationship between BAT and BMD in healthy adults.

Methods

BAT volume (ml) and activity (standard uptake value) were determined by ¹⁸F-fluorodeoxyglucose PET after overnight mild cold exposure at 19 °C, and BMD was determined by DXA.

Results

Among 24 healthy adults (age 28?±?1 years, F?=?10), BAT volumes were 82.4?±?99.5 ml in women and 49.7?±?54.5 ml in men. Women manifested significantly higher BAT activity, by 9.4?±?8.1 % (p?=?0.03), than men. BAT volume correlated positively with total and spine BMD (r ²?=?0.40 and 0.49, respectively, p?<?0.02) in women and remained a significant predictor after adjustment for age, fat, and lean body mass (p?<?0.05). Total and spine BMD were higher in women who harbored visually detectable BAT on PET images than those without by 11?±?2 % (p?=?0.02) and 22?±?2 % (p?<?0.01), respectively. No associations were observed between BAT parameters and BMD in men.

Conclusions

This study demonstrated higher BMD among healthy women with more abundant BAT, independent of age and other body compositional parameters. This was not observed in men. The data suggest that brown adipogenesis may be physiologically related to modulation of bone density.     

Physical Performance Variables and Bone Mineral Density in a Group of Young Overweight and Obese Men

The aim of this study was to explore the relationships between performances obtained in different physical tests and bone parameters (bone mineral density [BMD], bone mineral content, hip geometry indices, and trabecular bone score [TBS]) in a group of young Lebanese overweight and obese adult men. Fifty-two overweight and/or obese (body mass index?>?25?kg/m²) young men whose ages range from 18 to 35?yr participated in this study. Weight and height were measured, and body mass index was calculated. Body composition, BMD, cross-sectional area and section modulus (Z) of the femoral neck (FN), and TBS were measured by dual-energy X-ray absorptiometry. Maximum oxygen consumption (VO₂ max, in liter per minute) was determined by direct measurement while exercising on a medical treadmill. One-repetition-maximum half-squat and maximum power (P max) of the lower limbs were measured using validated exercises. Lean mass was a positive determinant of whole-body bone mineral content (r?=?0.71, p?<?0.001), FN cross-sectional area (r?=?0.51, p?<?0.001), and FN Z (r?=?0.58, p?<?0.001). VO₂ max (in liter per minute) was a positive determinant of whole-body BMD (r?=?0.47, p?<?0.001), total hip BMD (r?=?0.43, p?<?0.01), and FN BMD (r?=?0.42, p?<?0.01). VO₂ max (in milliliter per minute per kilogram) was a positive determinant of TBS (r?=?0.30, p?<?0.05). One repetition maximum was a positive determinant of L1–L4 BMD (r?=?0.33, p?<?0.05). This study suggests that VO₂ max (in liter per minute) is a positive determinant of BMD, and VO₂ max (in milliliter per minute per kilogram) is a positive determinant of TBS in overweight and obese men.     

Sclerostin serum levels in prostate cancer patients and their relationship with sex steroids

Summary

The role of sclerostin on bone metabolism and its relation to sex steroids in patients with prostate cancer (PC) is not well known. We found that sclerostin levels are significantly increased in PC patients, particularly in those with androgen deprivation therapy (ADT), and there is an inverse relationship between sclerostin levels and testosterone.

Introduction

Recent studies have evaluated sclerostin levels in bone diseases as osteoporosis. However, there are few data in PC patients, particularly in patients with hypogonadism related to ADT. The aim of the present study was to compare serum sclerostin levels in ADT/non-ADT-treated PC patients and healthy controls and to evaluate their relationship with sex steroids and bone metabolism.

Methods

We performed a cross-sectional study involving 81 subjects: 25 ADT-treated PC patients, 34 PC patients without ADT treatment, and 22 healthy controls. We measured serum sclerostin levels, bone turnover markers, bone mineral density (BMD) in all individuals, and sex steroids levels in PC patients.

Results

Serum sclerostin levels were significantly higher in PC patients compared to those in control subjects. ADT-treated patients had significantly higher sclerostin levels than PC patients without ADT treatment: ADT 64.52?±?27.21 pmol/L, non-ADT 48.24?±?15.93 pmol/L, healthy controls 38.48?±?9.19 pmol/L, p?<?0.05. In PC patients, we found a negative relationship between serum sclerostin levels and androgens after age adjustment (total testosterone: r?=??0.309, p?=?0.029; bioavailable testosterone: r?=??0.280, p?=?0.049; free testosterone: r?=??0.299, p?=?0.035). We did not observe any relationship between sclerostin levels and bone turnover markers or BMD in any group.

Conclusions

Circulating sclerostin levels are significantly increased in patients with PC and particularly in those receiving ADT. The inverse relationship between serum sclerostin and testosterone in these patients suggests that androgens are key regulators of bone metabolism in this population.     

Fibroblast growth factor 21 (FGF21) and bone: is there a relationship in humans?

Summary

In animals, high fibroblast growth factor 21 (FGF21) states improve insulin resistance but induce bone loss. Whether FGF21 relates to bone mineral density (BMD) is unknown in humans. Contrary to prediction from animal findings, we found higher FGF21 levels associating with greater BMD in women, independent of age and body composition.

Introduction

Recent laboratory studies suggest that FGF21 is involved in reciprocal regulation of bone and energy homeostasis. Systemic administration of FGF21 protects animals from obesity and diabetes but causes severe bone loss, smothering the enthusiasm over FGF21 as a potential antiobesity therapeutic. To date, there is no information on whether FGF21 relates to BMD in humans. We thus studied the relationship between plasma FGF21 levels and BMD in healthy adults.

Methods

Fasting plasma FGF21 levels were measured by enzyme-linked immunosorbent assay and body composition by dual-energy X-ray absorptiometry.

Results

Among 40 healthy volunteers (age 32?±?10 year, 16 women), men had significantly higher lean body mass (p?<?0.01) and total BMD (p?<?0.05), and lower percent body fat than women (p?<?0.01). Median plasma FGF21 levels were not different between the sexes. While there was no association between FGF21 concentrations and body composition in men, FGF21 levels correlated positively with fat mass (p?<?0.01) in women. In men, no significant correlation between FGF21 with BMD was observed. However, in women, FGF21 correlated positively with total BMD (R ²?=?0.69, p?=?0.003) and spine BMD (R ²?=?0.76, p?=?0.001); the correlation remained significant after adjusting for age, ethnicity, and body composition.

Conclusions

This study reveals for the first time a strong positive association between plasma FGF21 levels and BMD in healthy women, suggesting the association between bone loss and high FGF21 states in animals may not be directly translated to humans in physiologic states. We hypothesize that FGF21 may increase bone mass particularly in women through paracrine mechanisms in the bone–adipose interface.     

The relationship between pulmonary function and bone mineral density in healthy nonsmoking women: the Korean National Health and Nutrition Examination Survey (KNHANES) 2010

Summary

The aim of this study was to examine the association between pulmonary function and bone mineral density (BMD) in subjects who had never smoked. Pulmonary function was associated with BMD in premenopausal, but not postmenopausal, women.

Introduction

It has been reported that low bone mass is common in patients with pulmonary disorders such as chronic obstructive pulmonary disease. However, in healthy nonsmoking women, the relationship between bone mass and pulmonary function has yet to be clarified. The object of this study was to determine whether pulmonary function is related to BMD in healthy nonsmoking women based on menopausal status.

Methods

This study was a cross-sectional study based on data obtained from the Korean National Health and Nutrition Examination Survey (KNHANES), a nationwide representative survey conducted by the Korean Ministry of Health and Welfare in 2010. This study included 456 subjects who had never smoked and analyzed data concerning pulmonary function and BMD.

Results

Functional vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were correlated with BMD at lumbar spine, femur neck (FN), and total hip in premenopausal women (p = 0.030, p = 0.003, p = 0.019, respectively, for FVC; p = 0.015, p = 0.006, p = 0.059, respectively, for FEV₁). However, FVC and FEV₁ were only correlated with BMD at FN in postmenopausal women (p = 0.003 for FVC; p = 0.006 for FEV₁). Body mass index (BMI), FVC, and FEV₁ were significantly related with BMD at FN, even after adjusting for age and other confounding factors (β = 0.334, p < 0.001; β = 0.145, p = 0.017; and β = 0.129, p = 0.037, respectively) in premenopausal women. However, only age and BMI were correlated with BMD at FN (β = ?0.268, p = 0.001 and β = 0.384, p > 0.001) in postmenopausal women after adjusting for confounding factors.

Conclusions

Pulmonary function, including FVC and FEV₁ are associated with BMD at FN in healthy nonsmoking premenopausal women but not in postmenopausal women.     

Polymorphisms and haplotypes across the osteoprotegerin gene associated with bone mineral density and osteoporotic fractures

Summary

Osteoprotegerin plays a key role in bone remodelling. We studied the association between 24 polymorphisms and haplotypes on the OPG gene and bone mineral density and fractures. After multiple-testing correction, one SNP and two block-haplotypes were significantly associated with FN BMD. Two other block-haplotypes were associated with fracture.

Introduction and Hypothesis

Osteoprotegerin (OPG) plays a key role in bone remodelling. Here we studied the association between polymorphisms and haplotypes on the OPG gene and bone mineral density (BMD) and fractures.

Methods

Twenty-four single nucleotide polymorphisms (SNPs) were selected to cover six haplotypic blocks and were genotyped in 964 postmenopausal Spanish women. Haplotypes were established with HaploStats. Association was analysed by GLM (for BMD) and logistic regression (for fractures) both at single SNP and haplotype levels.

Results

Upon adjustment for multiple testing (p?<?0.0073), one of the SNPs (SNP #17, rs1032129) remained significantly associated with FN BMD (p?=?0.001). Four block-haplotypes stood multiple-testing correction. Two remained associated with FN BMD and two with fracture. The association of block-4 haplotype “AC” (of SNPs #18 and #17) with FN BMD (p?=?0.0002) was stronger than that of SNP#17 alone and was the best result overall. A global assessment of the results indicated that all the alleles and haplotypes with a protective effect, at p?<?0.05, belonged to a frequent long-range haplotype.

Conclusions

In conclusion, these results provide a detailed picture of the involvement of common variants and haplotypes of the OPG gene in bone phenotypes.     

Physical activity, calcium intake and childhood bone mineral: a population-based cross-sectional study

Summary

In a free-living cohort of 4-year old children, mean daily time in moderate?Cvigorous physical activity and daily calcium intake at 3?years, were positively related to hip bone size and density. Relationships between physical activity and bone indices were stronger when calcium intake was above compared with below median (966?mg/day).

Introduction

We examined the cross-sectional relationships between childhood physical activity, dietary calcium intake and bone size and density.

Methods

Children aged 4?years were recruited from the Southampton Women's Survey. They underwent measurement of bone mass by DXA (Hologic Discovery). Physical activity was assessed by accelerometry (Actiheart, Cambridge Neurotechnology Ltd, Cambridge, UK) for seven continuous days.

Results

Four hundred twenty-two children (212 boys) participated. In a cross-sectional analysis, after adjusting for gender, daily mean time(minutes per day) spent in moderate to very vigorous activity (MVPA) was positively related to hip BA (R ²?=?3%, p?<?0.001), BMC (R ²?=?4%, p?<?0.001), aBMD (R ²?=?3%, p?=?0.001) and estimated vBMD (R ²?=?2%, p?=?0.01), but not height (r _s?=?0.04, p?=?0.42) or weight (r _s?=?0.01, p?=?0.76). Mean daily calcium intake (assessed at 3?years old) positively predicted bone indices in those with a calcium intake below the median (966?mg/day), but there was a much attenuated relationship in those above this. These associations persisted after inclusion of total energy, protein and phosphorus in multivariate models. The relationships between MVPA and bone indices were stronger in children with calcium intakes above the median. Thus, for aBMD, the variance explained by MVPA when daily calcium intake was below the median was 2% (p?=?0.1) and above median was 6% (p?=?0.001).

Conclusions

These results support the notion that adequate calcium intake may be required for optimal action of physical activity on bone development and that improving levels of physical activity and calcium intake in childhood may help to optimise accrual of bone mass.     

Association of P2X7 receptor polymorphisms with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients

Summary

The P2X₇ receptor is thought to be involved in bone physiology in a pro-osteogenic manner. Therefore, we examined associations between genetic variations in the P2X₇ receptor gene and bone mineral density (BMD). We found an association between four non-synonymous polymorphism of the human P2X₇ receptor and the risk of osteoporosis.

Introduction

The purpose of this study was to determine whether genetic variation in the P2X₇ receptor gene (P2RX7) is associated with decreased BMD and risk of osteoporosis in fracture patients.

Methods

Six hundred ninety women and 231 men aged ≥50 years were genotyped for 15 non-synonymous P2RX7 SNPs. BMD was measured at the total hip, lumbar spine and femoral neck.

Results

Four non-synonymous SNPs were associated with BMD. The Ala348Thr gain-of-function polymorphism was associated with increased BMD values at the lumbar spine (p?=?0.012). Decreased hip BMD values were associated with two loss-of-function SNPs in the P2RX7, i.e., in subjects homozygous for the Glu496Ala polymorphism as well as in subjects carrying at least one variant allele of the Gly150Arg polymorphism (p?=?0.018 and p?=?0.011; respectively). In men, we showed that subjects either heterozygous or homozygous for the Gln460Arg gain-of-function polymorphism in the P2RX7 had a significantly 40 % decrease in risk of a lower T-score value (OR?=?0.58 [95%CI, 0.33–1.00]).

Conclusion

Thus, genetic aberrations of P2X7R function are associated with lower BMD and increased osteoporosis risk. Therefore, detection of non-synonymous SNPs within the P2RX7 might be useful for osteoporosis risk estimation at an early stage, potentially enabling better osteoporosis prevention and treatment.     

The rhPTH treatment elevates plasma secreted protein acidic and rich in cysteine levels in patients with osteoporosis

Summary

The secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin, plays an important role in osteoblast formation, maturation, and survival. Here, we report the effects of recombinant human parathyroid hormone (1-34) [rhPTH (1-34)], a bone formation-stimulating agent, and elcatonin on plasma SPARC levels in patients with osteoporosis. The rhPTH (1-34) treatment significantly increased plasma SPARC levels, and the change of plasma SPARC correlated positively with changes of lumbar bone mineral density (BMD) at L2–L4. These results unveil that SPARC may be a novel marker related to the regulation of bone formation.

Introduction

rhPTH (1-34) is known to influence osteoclast maturation and activity through modulation of osteoblast-derived cytokines. SPARC is the most abundant noncollagenous extracellular matrix protein in the bone. So far, however, no study has reported the effects of rhPTH (1-34) administration on plasma SPARC levels in patients with osteoporosis. The purpose of this study was to compare the response of SPARC and BMD to rhPTH (1-34) and elcatonin in postmenopausal women with osteoporosis.

Methods

Women were randomized to either once-daily subcutaneous injection of rhPTH (1-34) (20 μg, N?=?89) or once-weekly intramuscular injection of elcatonin (200 U, N?=?35) for 12 months. Plasma biochemical markers of bone turnover and BMD were measured at baseline, 6 and 12 months after treatment.

Results

At baseline, plasma SPARC levels correlated positively with lumbar spine BMD in all patients (r?=?0.45, p?=?0.001). Compared with baseline, at 12 months, rhPTH (1-34) significantly increased lumbar spine BMD and plasma SPARC levels (p?=?0.008 and p?=?0.001, respectively), whereas elcatonin was ineffective. More importantly, the changes of plasma SPARC correlated positively with changes of lumbar BMD at L2–L4 (r?=?0.47, p?=?0.001) in the rhPTH (1-34)-treated group, but not in the elcatonin group.

Conclusion

The increase in plasma SPARC levels during the rhPTH (1-34) treatment may have contributed to the anabolic effect on bone formation, and SPARC may be a novel marker related to the regulation of bone formation.     

The BPAQ: a bone-specific physical activity assessment instrument

Summary  A newly developed bone-specific physical activity questionnaire (BPAQ) was compared with other common measures of physical activity for its ability to predict parameters of bone strength in healthy, young adults. The BPAQ predicted indices of bone strength at clinically relevant sites in both men and women, while other measures did not. Introduction  Only certain types of physical activity (PA) are notably osteogenic. Most methods to quantify levels of PA fail to account for bone relevant loading. Our aim was to examine the ability of several methods of PA assessment and a new bone-specific measure to predict parameters of bone strength in healthy adults. Methods  We recruited 40 men and women (mean age 24.5). Subjects completed the modifiable activity questionnaire, Bouchard 3-day activity record, a recently published bone loading history questionnaire (BLHQ), and wore a pedometer for 14 days. We also administered our bone-specific physical activity questionnaire (BPAQ). Calcaneal broadband ultrasound attenuation (BUA) (QUS-2, Quidel) and densitometric measures (XR-36, Norland) were examined. Multiple regression and correlation analyses were performed on the data. Results  The current activity component of BPAQ was a significant predictor of variance in femoral neck bone mineral density (BMD), lumbar spine BMD, and whole body BMD (R² = 0.36–0.68, p < 0.01) for men, while the past activity component of BPAQ predicted calcaneal BUA (R² = 0.48, p = 0.001) for women. Conclusions  The BPAQ predicted indices of bone strength at skeletal sites at risk of osteoporotic fracture while other PA measurement tools did not.     

Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study

Summary

Sclerostin is a key regulator of bone formation. In a population of 572 postmenopausal women (mean age, 67 years) followed prospectively for a median of 6 years, there was no significant association between baseline levels of serum sclerostin and incidence of all fractures which occurred in 64 subjects.

Introduction

Sclerostin, an osteocyte soluble factor, is a major negative regulator of osteoblastic activity. Circulating sclerostin levels were reported to increase with age and to be modestly associated with bone mineral density (BMD) and bone turnover, but there are no data on the association with fracture risk.

Methods

We investigated 572 postmenopausal women (mean age, 67?±?8.5 years) from the OFELY population-based cohort. The associations of serum sclerostin measured with a new two-site ELISA and spine and hip BMD by DXA, serum β-isomerized C-terminal crosslinking of type I collagen (CTX), intact N-terminal propeptide of type I collagen (PINP), intact PTH, 25-hydroxyvitamin D [25(OH)D], estradiol, testosterone, and fracture risk were analyzed. At the time of sclerostin measurements, 98 postmenopausal women had prevalent fractures. After a median of 6 years (interquartile range, 5–7 years) follow-up, 64 postmenopausal sustained an incident fracture.

Results

Serum sclerostin correlated positively with spine (r?=?0.35, p?<?0.0001) and total hip (r?=?0.25, <0.0001) BMD. Conversely, serum sclerostin was weakly negatively associated with the bone markers PINP (r?=??0.10, p?=?0.014) and CTX (r?=??0.13, p?=?0.0026) and with intact PTH (r?=??0.13, p?=?0.0064). There was no significant association of serum sclerostin with 25(OH)D, estradiol, free estradiol index, or testosterone. Serum sclerostin considered as a continuous variable or in quartiles was not significantly associated with the risk of prevalent or incident fracture.

Conclusion

Serum sclerostin is weakly correlated with BMD, bone turnover, and PTH in postmenopausal women. It was not significantly associated with the risk of all fractures, although the number of incident fractures recorded may not allow detecting a modest association.     

Birth weight is more important for peak bone mineral content than for bone density: the PEAK-25 study of 1,061 young adult women

Summary

Lower birth weight has a negative association with adult BMC and body composition in young adult Swedish women.

Introduction

The aim of this study was to evaluate the influence of birth weight on peak bone mass and body composition in a cohort of 25-year-old women.

Methods

One thousand sixty-one women participated in this cross-sectional population-based study using dual energy X-ray absorptiometry (DXA) to assess bone mineral content (BMC), bone mineral density (BMD), and body composition (total body (TB), femoral neck (FN), total hip (TH), lumbar spine L1–L4 (LS), and lean and fat mass). Birth weight data was available for 1,047 women and was categorized into tertiles of low (≤3,180 g), intermediate (3,181–3,620 g), and high (≥3,621 g) birth weight.

Results

Significant correlations were observed between birth weight and TB-BMC (r?=?0.159, p?<?0.001), FN-BMC (r?=?0.096, p?<?0.001), TH-BMC (r?=?0.102, p?=?0.001), LS-BMC (r?=?0.095, p?=?0.002), and lean mass (r?=?0.215, p?<?0.001). No correlation was observed between birth weight and BMD. The estimated magnitude of effect was equivalent to a 0.3–0.5 SD difference in BMC for every 1 kg difference in birth weight (151 g (TB); 0.22 g (FN); 1.5 g (TH), 2.5 kg TB lean mass). The strongest correlations between birth weight and BMC occurred in women with lowest birth weights, although excluding women who weighed <2,500 g at birth, and the correlation remained significant although slightly weaker.

Conclusions

Women with lower birth weight have lower BMC and less lean and fat mass at the age of 25, independent of current body weight. Lower birth weight has a greater negative influence on bone mass than the positive influence of higher birth weight.     

Alterations of bone microstructure and strength in end-stage renal failure

Summary

End-stage renal disease (ESRD) patients have a high risk of fractures. We evaluated bone microstructure and finite-element analysis-estimated strength and stiffness in patients with ESRD by high-resolution peripheral computed tomography. We observed an alteration of cortical and trabecular bone microstructure and of bone strength and stiffness in ESRD patients.

Introduction

Fragility fractures are common in ESRD patients on dialysis. Alterations of bone microstructure contribute to skeletal fragility, independently of areal bone mineral density.

Methods

We compared microstructure and finite-element analysis estimates of strength and stiffness by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 33 ESRD patients on dialysis (17 females and 16 males; mean age, 47.0?±?12.6 years) and 33 age-matched healthy controls.

Results

Dialyzed women had lower radius and tibia cortical density with higher radius cortical porosity and lower tibia cortical thickness, compared to controls. Radius trabecular number was lower with higher heterogeneity of the trabecular network. Male patients displayed only a lower radius cortical density. Radius and tibia cortical thickness correlated negatively with bone-specific alkaline phosphatase (BALP). Microstructure did not correlate with parathyroid hormone (PTH) levels. Cortical porosity correlated positively with “Kidney Disease: Improving Global Outcomes” working group PTH level categories (r?=?0.36, p?<?0.04). BMI correlated positively with trabecular number (r?=?0.4, p?<?0.02) and negatively with trabecular spacing (r?=??0.37, p?<?0.03) and trabecular network heterogeneity (r?=??0.4, p?<?0.02). Biomechanics positively correlated with BMI and negatively with BALP.

Conclusion

Cortical and trabecular bone microstructure and calculated bone strength are altered in ESRD patients, predominantly in women. Bone microstructure and biomechanical assessment by HR-pQCT may be of major clinical relevance in the evaluation of bone fragility in ESRD patients.     

Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D

Summary

Androgen deprivation therapy in 80 men was associated with declines in bone mineral density (BMD), which were greatest in the first year, and in the lumbar spine compared to controls. Vitamin D use was associated with improved BMD in the lumbar spine and in the first year.

Introduction

Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased risk of fractures. Although loss of BMD appears to be greatest within the first year of starting ADT, there are few long-term studies of change in BMD, and risk factors for bone loss are not well-characterized.

Methods

Men aged 50+ with nonmetastatic prostate cancer starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. Matched controls were men with prostate cancer not receiving ADT. Multivariable regression analysis examined predictors of BMD loss.

Results

Eighty ADT users and 80 controls were enrolled (mean age 69 years); 52.5 % had osteopenia and 8.1 % had osteoporosis at baseline. After 1 year, in adjusted models, ADT was associated with significant losses in lumbar spine BMD compared to controls (?2.57 %, p?=?0.006), with a trend towards greater declines at the total hip (p?=?0.09). BMD changes in years 2 and 3 were much smaller and not statistically different from controls. Use of vitamin D but not calcium was associated with improved BMD in the lumbar spine in year 1 (+6.19 %, p?<?0.001) with smaller nonsignificant increases at other sites (+0.86 % femoral neck, +0.86 % total hip, p?>?0.10) primarily in the first year.

Conclusions

Loss of BMD associated with ADT is greatest at the lumbar spine and in the first year. Vitamin D but not calcium may be protective particularly in the first year of ADT use.     

Bone loss in relation to serum levels of osteoprotegerin and nuclear factor-κB ligand: the Tromsø Study

Summary

In this longitudinal study of 4,137 persons, bone mineral density was negatively associated with osteoprotegerin at baseline in both genders. In postmenopausal women not using hormone replacement therapy (HRT), bone-loss increased with increasing osteoprotegerin levels, whereas no relationship was found in men, premenopausal women, or postmenopausal women taking HRT.

Introduction

In a population-based study of 2,003 men and 2,134 women, the relationship between the osteoprotegerin (OPG)/factor-κB ligand (RANKL) system and bone mineral density (BMD) and changes in BMD was examined.

Methods

Baseline measurements included height, weight, BMD of the forearm, OPG, RANKL, vitamin D, and serum parathyroid hormone (PTH) and information about lifestyle, prevalent diseases, and use of medication. BMD was remeasured at follow-up 6 years later.

Results

BMD was negatively associated with OPG at baseline in both men and women (p trend over OPG levels?=?0.01 and 0.007, respectively, after adjustments for age, and other confounders). In postmenopausal women not on hormone replacement therapy, bone loss increased with increasing OPG (p?=?0.005), whereas no relationship was found in men, premenopausal women, or postmenopausal women on HRT (p?≥?0.28). BMD at baseline and BMD changes were not related to RANKL levels in any of the groups (p?≥?0.14).

Conclusions

In postmenopausal women not using HRT, bone loss associated positively with OPG. The results indicate that in women deficient in sex steroids, the OPG/RANKL system may play an important counter regulatory role in order to avoid bone loss and maintain BMD. In men and women replete in sex steroids, the OPG/RANKL system was not associated with BMD.