Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial

Summary

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength.

Introduction

To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength.

Methods

In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated.

Results

Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p?<?0.01) and QCT (5.7%, p?<?0.0001). Between-treatment differences were significant for trabecular spine (p?=?0.0017) [non-parametric test], trabecular trochanter (10.7%, p?<?0.0001), total hip (10.8%, p?<?0.0001), and compressive strength indices at femoral neck (8.6%, p?=?0.0001), and trochanter (14.1%, p?<?0.0001).

Conclusions

Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.     

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.     

BMD improvements after operation for primary hyperparathyroidism

Purpose

This study aims to quantify bone mineral density (BMD) changes following surgery in patients with primary hyperparathyroidism (PHPT) and to assess their relationship with clinical and biochemical variables.

Methods

A historic cohort of 236 PHPT patients with DXA scans pre- and 1-year postoperatively, clinical data, and biochemical data was analyzed.

Results

The mean age was 60 years (range 19–86) and 81 % of the patients were women. A significant postoperative 2.6 % (95 % CI, 2.1; 3.1) increase in lumbar spine BMD was seen. The increase in BMD was positively associated with preoperative plasma PTH (p?=?0.002), Ca²⁺ (p?<?0.001), and alkaline phosphatase (p?=?0.014). Hip BMD increased 1.5 % (1.1; 1.9). The increase in BMD was positively associated with preoperative plasma PTH (p?=?0.005) and Ca²⁺ (p?<?0.001) and inversely associated with plasma creatinine (p?=?0.004) and age (p?=?0.018). Total forearm BMD did not change significantly (?0.2 % (?0.5; 0.1)). An increase in forearm BMD was seen in 38 % of all patients, and the changes were positively associated with plasma PTH (p?<?0.001) and Ca²⁺ (p?=?0.009). In all 91 patients with mild PHPT (plasma Ca²⁺?<?1.45 mmol/l), there was a significant postoperative increase in spine BMD (1.9 % (1.2; 2.7)) and in hip BMD (1.0 % (0.4; 1.6)), but not in the forearm BMD (?0.3 % (?0.7; 0.2)). The postoperative BMD gain was higher in the hip and forearm in patients operated for adenomas compared with patients treated for hyperplasia.

Conclusions

We found significant postoperative BMD improvements both at the hip and the spine. BMD improvements were also significant in mild cases. At all scan sites, there were positive associations between preoperative plasma PTH levels and postoperative BMD increases. The measured BMD changes may mainly be due to a decrease in PTH-induced bone turnover with refilling of the remodeling space.     

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.     

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.     

Polymorphisms in the ALOX12 gene and osteoporosis

Summary

ALOX12 produces ligands for PPAR?? thereby turning mesenchymal stem cells into adipocytes instead of osteoblasts. We investigated the effect of polymorphisms in the ALOX12 gene on BMD and fracture risk in two Danish cohorts and found four polymorphisms and a haplotype thereof to be associated with BMD and fracture risk.

Introduction

Stimulation of the PPAR?? with ligands produced by the ALOX enzymes drives mesenchymal stem cells in an adipocyte direction at the expense of osteoblasts leading to decreased osteoblast number and BMD. Previously, polymorphisms in the ALOX12 gene have been associated with osteoporosis.

Methods

We examined the effect of ALOX12 polymorphisms on BMD and the risk of fractures in two Danish cohorts: AROS, a case?Ccontrol population comprising 809 individuals and DOPS, a population comprising 1,716 perimenopausal women allocated to hormone therapy or not at baseline and followed for up to 10?years. On the basis of linkage disequilibrium (LD) between SNPs throughout the gene and previous genetic association studies we chose ten polymorphisms for investigation. Genotyping was carried out using the Sequenom MassARRAY genotyping system and TaqMan assays.

Results

In AROS, individuals heterozygous for the polymorphisms rs3840880, rs9897850, rs2292350 and rs1126667 had a 3.0?C4.7% decreased lumbar spine BMD (p?=?0.02?C0.06) and an increased risk of vertebral fractures (p?<?0.05) compared with individuals homozygous for either allele. In DOPS, none of the individual SNPs were associated with BMD or incident fractures. In both cohorts, the above-mentioned SNPs comprised an LD-block (pairwise D???=?1.0, r ²?=?0.45?C0.97). A haplotype comprising all the common alleles (frequency 9%) was associated with decreased bone loss at the hip (p?<?0.05) and decreased incidence of osteoporotic fractures (p?<?0.05) in DOPS and increased femoral neck BMD in AROS (p?<?0.05).

Conclusion

Our study suggests that genetic variants in ALOX12 may influence BMD and fracture risk.     

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 BPAQ-derived physical activity and bone density of middle-aged and older men

Summary

The bone-specific physical activity questionnaire (BPAQ) accounts for activities that affect bone but has not been used in studies with older adults. Relationships exist between the BPAQ-derived physical activity and bone density in healthy middle-aged and older men but not men with prostate cancer. Disease-related treatments detrimental to bone should be considered when administering the BPAQ.

Introduction

The bone-specific physical activity questionnaire (BPAQ) was developed to account for bone-specific loading. In this retrospective study, we examined the relationship between BPAQ-derived physical activity and bone mineral density (BMD) in middle-aged and older men with and without prostate cancer.

Methods

Two groups, 36 healthy men and 69 men with prostate cancer receiving androgen suppression therapy (AST), completed the BPAQ and had whole body, total hip, femoral (FN) and lumbar spine BMD assessed by dual-energy X-ray absorptiometry.

Results

Past (pBPAQ), current (cBPAQ) and total BPAQ (tBPAQ) scores for the healthy men were related to FN BMD (pBPAQ r?=?0.36, p?=?0.030; cBPAQ r _s?=?0.35, p?=?0.034; tBPAQ r?=?0.41, p?=?0.014), and pBPAQ and tBPAQ were related to total hip (r _s?=?0.35, p?=?0.035 and r _s?=?0.36, p?=?0.029, respectively) and whole body BMD (r _s?=?0.44, p?=?0.007 and r _s?=?0.45, p?=?0.006, respectively). In men with prostate cancer, the BPAQ was not significantly associated with BMD. In stepwise regression analyses, body mass and tBPAQ predicted 30 % of the variance in total hip BMD (p?=?0.003), cBPAQ predicted 14 % of the variance in FN BMD (p?=?0.002), and body mass, age and tBPAQ predicted 47 % of the variance in whole body BMD (p?Conclusions Although BPAQ-derived estimates of physical activity are related to bone status in healthy middle-aged and older men, the adverse effect of AST on bone appears to obscure this relationship in men with prostate cancer.     

Osteoporosis in Indian women aged 40–60 years

Summary

The study investigates BMD pattern in Indian women aged 40–60 years through a retrospective assessment using DEXA scan of hip and spine of 1,282 asymptomatic Indian women. The Study group indicated high incidence of decreased bone mass and significantly lower BMD as compared to western and other Asian counterparts.

Introduction

An understanding of BMD pattern in women aged 40–60 years is crucial for prevention, diagnosis of osteoporosis and management of its complications in later life. Hence, the present study investigates BMD in Indian women aged 40–60 years for which no data exists in literature.

Method

A retrospective assessment of BMD by DEXA scan of hip and spine of 1,282 asymptomatic women in age group 40–60 was performed. Standardized BMD was calculated and compared with other population groups.

Results

Osteoporosis and osteopenia are widely prevalent among females of the 40–60 age group as a meager 35% of subjects had normal bone density. Average BMD of spine was 0.89 (SD 0.14) gm/cm² and average BMD of hip was 0.85(0.15) gm/cm². The correlation between BMD and age was negative. Spine DEXA was found to be more significant than hip DEXA (p value?<?0.0001) for osteoporosis assessment. Similarly, T scores of spine were more significantly correlated in this age group (p value?<?0.0001) for osteoporosis than hip T scores.

Conclusion

The study group indicated high incidence of decreased bone mass, and significantly lower BMD as compared to western and other Asian counterparts. This study emphasizes on early screening and treatment in study group to avoid long-term complications.     

Impact + resistance training improves bone health and body composition in prematurely menopausal breast cancer survivors: a randomized controlled trial

Summary

Our randomized controlled trial in prematurely menopausal breast cancer survivors showed that impact + resistance training prevented increases in percentage of body fat compared with controls and also improved BMD at the hip and prevented BMD loss at the spine among exercise-trained women who were menopausal for >1 year.

Introduction

Cancer treatment-related menopause worsens bone health and body composition in breast cancer survivors (BCS). We investigated whether impact + resistance training could improve bone mineral density (BMD), reduce bone turnover, build muscle, and decrease fat mass in BCS with premature menopause.

Methods

We conducted a randomized controlled trial in 71 BCS (mean age, 46.5 years) within 5 years of treatment-related menopause. Women were randomly assigned to one of two groups: (1) impact + resistance training (prevent osteoporosis with impact + resistance (POWIR)) or (2) exercise placebo (FLEX) 3×/week for 1 year. Outcomes were hip and spine BMD (in grams per square centimeter) and body composition (percent body fat (%BF) and lean and fat mass (in kilograms)) by DXA and bone turnover markers (serum osteocalcin (in nanograms per milliliter) and urinary deoxypryrodinoline (in nanomoles per milliliter).

Results

There were no significant group × time interactions for bone outcomes when using an intent-to-treat approach on the full sample. In analyses restricted to BCS who were menopausal for ≥1 year, POWIR increased BMD at the hip and slowed BMD loss at the spine compared with FLEX (femoral neck—POWIR, 0.004?±?0.093 g/cm² vs. FLEX, ?0.010?±?0.089 g/cm²; p?<?0.01; spine—POWIR, ?0.003?±?0.114 g/cm² vs. FLEX, ?0.020?±?0.110 g/cm²; p?=?0.03). POWIR prevented increases in %BF (POWIR, 0.01 % vs. FLEX, 1.3 %; p?<?0.04). Women with attendance to POWIR at ≥64 % had better improvements in %BF than women attending less often (p?<?0.03).

Conclusion

Impact + resistance training may effectively combat bone loss and worsening body composition from premature menopause in BCS.     

Relationship of thoracic kyphosis and lumbar lordosis to bone mineral density in women

Summary

The relationship between spinal curvature and bone mineral density (BMD) in women was examined. Significant relationships were observed between spinal curvature and BMD in both pre- and postmenopausal women. Excessive spinal curvature may be associated with low bone mass in premenopausal women.

Introduction

The purpose of this study was to examine the associations between spinal measurements of thoracic and lumbar curvatures and bone mineral density in pre- and postmenopausal women.

Methods

The data for this study were obtained from the Texas Woman’s University Pioneer Project. Female participants (n?=?242; premenopausal n?=?104, postmenopausal n?=?138) between the ages of 18 and 60 years were evaluated on multiple health measures. Thoracic and lumbar curvatures were measured with a 24-in. (60 cm) flexicurve. Bone mineral density was assessed via dual-energy X-ray absorptiometry (Lunar DPX IQ, version 4.6e). Pearson correlations and logistic regression analysis were used to examine the associations between the obtained spinal curvature measurements and bone mineral density. Significance was set at p?<?.05.

Results

Significant correlations were observed for the femoral neck and lumbar spine bone mineral density with thoracic and lumbar curve in premenopausal women (r?=??.344 to???.525; p?<?.001). Slightly weaker, but significant, correlations were observed for femoral neck and lumbar spine in relation to thoracic and lumbar curve in postmenopausal women (r?=??.288 to ?.397; p?<?.01). Premenopausal women with thoracic curvature greater than 4 cm had a greater risk of having low bone mass compared to premenopausal women with less than 4 cm of curvature (odds ratio?=?3.982, 95 % CI?=?1.206, 13.144).

Conclusions

The observed negative relationship suggests that as either thoracic or lumbar curvature increases, the regional bone mineral density decreases in both pre- and postmenopausal women.     

Regional bone metabolism at the lumbar spine and hip following discontinuation of alendronate and risedronate treatment in postmenopausal women

Summary

The aim of this study was to examine the effects of bisphosphonate discontinuation on bone metabolism at the spine and hip measured using ¹⁸?F-fluoride PET. Bone metabolism at the spine remained stable following discontinuation of alendronate and risedronate at 1?year but increased in the hip in the alendronate group only.

Introduction

Bisphosphonates such as alendronate (ALN) or risedronate (RIS) have persistent effects on spine BMD following discontinuation.

Methods

Positron emission tomography (PET) was used to examine regional bone metabolism in 20 postmenopausal women treated with ALN (n?=?11) or RIS (n?=?9) for a minimum of 3?years at screening (range 3–9?years, mean 5?years for both groups). Subjects underwent a dynamic scan of the lumbar spine and a static scan of both hips at baseline and 6 and 12?months following treatment discontinuation. ¹⁸?F-fluoride plasma clearance (K_i) at the spine was calculated using a three-compartment model. Standardised uptake values (SUV) were calculated for the spine, total hip, femoral neck and femoral shaft. Measurements of BMD and biochemical markers of bone turnover were also performed.

Results

With the exception of a significant decrease in spine BMD in the ALN group, BMD remained stable. Bone turnover markers increased significantly from baseline by 12?months for both study groups. Measurements of K_i and SUV at the spine and femoral neck did not change significantly in either group. SUV at the femoral shaft and total hip increased significantly but in the ALN group only, increasing by 33.8% (p?=?0.028) and 24.0% (p?=?0.013), respectively.

Conclusions

Bone metabolism at the spine remained suppressed following treatment discontinuation. A significant increase in SUV at the femoral shaft and total hip after 12?months was observed but for the ALN group only. This study was small, and further clinical studies are required to fully evaluate the persistence of BP treatment.     

International variation in proximal femur bone mineral density

Summary

We observed higher proximal femur bone mineral density (BMD) in European women compared to average values derived from US Caucasian women in the National Health and Nutrition Examination Survey (NHANES) study. Across European centres, Parisian women had lower proximal femur BMD compared to women from Kiel or Sheffield.

Introduction

Proximal femur BMD of US adults (NHANES III) may not accurately reflect that of European women. We examined the heterogeneity of BMD across European and US Caucasian women and across different European populations.

Methods

Proximal femur BMD was measured in women ages 20–39 years (n?=?258) and 55–79 years (n?=?1,426) from three European centres. Cross-calibrated BMD for total hip, femoral neck, trochanter and intertrochanter were examined. International variation in BMD was assessed by comparing means and SDs in the European data with those from the US NHANES III study. European populations were stratified into 5-year age bands to establish individual centre reference intervals. Between-centre differences were assessed using ANOVA and post hoc Fisher’s least significant difference tests.

Results

European women had higher BMD than US women: The differences were 7.1% to 14.2% (p?<?0.001) and 0% to 3.9% (p?<?0.05) in the older and younger women, respectively. Standard deviations for BMD at the different sites were comparable to those for US women. Among older, but not younger European women, proximal femur BMD was significantly lower in French women (Paris) than in women from Germany (Kiel) or the UK (Sheffield) (difference?=?5.0% to 9.6%, p?<?0.05).

Conclusions

International variation in hip BMD does exist, with international and between-centre differences being less evident at the femoral neck.     

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.     

An investigation of the association between omega 3 FA and bone mineral density among older adults: results from the National Health and Nutrition Examination Survey years 2005–2008

Summary

The relation of omega 3 fatty acids (n-3 FA) with bone mineral density (BMD) was assessed among adults >60 years; NHANES data (2005–2008). The association of dietary n-3 FA with measures of hip BMD was equivocal, but n-3 FA supplement use was significantly associated with higher spine BMD—a finding that deserves further study.

Introduction

Associations between polyunsaturated fatty acids and bone mineral density are not well understood.

Purpose

To evaluate the cross-sectional relation between dietary omega 3 fatty acid intake (specifically docosahexaenoic acid, eicosapentaenoic acid, and octadecatetraenoic) and BMD at the hip and spine among older adults.

Methods

Omega 3 FA intake (g/day) was assessed from two 24-h recalls using the National Health and Nutrition Examination Survey (NHANES, in 2005–2008); and omega 3 FA supplement use (yes/no) via questionnaire. Multivariable regression models were developed to explain variance in femoral neck, total femur, and lumbar spine BMD among 2,125 men and women over 60 years.

Results

Mean age was 70 years. In adjusted models, dietary omega 3 FA were marginally associated with greater femoral neck BMD (p?=?0.0505), but not with total femur BMD (p?=?0.95) or lumbar spine BMD (p?=?0.74). Omega 3 supplement use was significantly positively associated with lumbar spine BMD (p?=?0.005) but not with femoral neck or total femur BMD.

Conclusions

Dietary intakes of omega 3 FA were marginally associated with femoral neck BMD; however, omega 3 supplement use was significantly associated with higher lumbar spine BMD in older adults. These results emphasize the need for assessment of total omega 3 intakes (diet and supplements) to provide a greater range of intake and a more accurate picture of the relation between omega 3 FA and BMD.     

Use of risedronate to prevent bone loss following a single course of glucocorticoids: findings from a proof-of-concept study in inflammatory bowel disease

Summary

We performed a randomised controlled trial (RCT) to determine whether risedronate 35 mg once weekly prevents bone loss following an 8-week reducing course of prednisolone given for an exacerbation of inflammatory bowel disease (IBD). The greatest change in bone mineral density (BMD) was at Ward’s triangle (WT), which fell by 2.2% in the placebo group, compared with a reduction of 0.8% in the risedronate group.

Introduction

Whether bisphosphonates can prevent bone loss associated with intermittent glucocorticoid (GC) therapy is unknown, reflecting the difficulty in performing RCTs in this context.

Method

To explore the feasibility of RCTs to examine this question, lumbar spine (LS; L2–4) and hip dual X-ray absorptiometry (DXA) scans were performed in 78 patients commencing a GC therapy course for a relapse of IBD. They were then randomised to receive placebo or risedronate 35 mg weekly for 8 weeks, after which the DXA scan was repeated.

Results

For LS BMD, there was no change in the placebo group (0.1?±?0.4, p?=?0.9), but there was an increase after risedronate (0.8?±?0.4, p?=?0.04; mean%?±?SEM by paired Student’s t test). There were small decreases in both groups at the total hip (?0.5?±?0.3, p?=?0.04; ?0.5?±?0.3, p?<?0.05, placebo and risedronate, respectively). At WT, BMD fell after placebo (?2.2?±?0.5, p?=?0.001) but not risedronate (?0.8?±?0.5, p?=?0.09; p?=?0.05 for between-group comparison).

Conclusion

RCTs can be used to examine whether bisphosphonates prevent bone loss associated with intermittent GC therapy, providing metabolically active sites such as WT are employed as the primary outcome.     

Functional fitness and bone mineral density in the elderly

Summary

Bone quality has been associated with genetic factors and several environmental influences. This study suggests that although functional fitness should be considered in clinical assessments of bone health, body composition appears to have a higher relevance in the explanation of bone health/strength in older people.

Purpose

This study aims to describe the association between functional fitness (FF), other constitutive factors, and bone health/strength in a large community-dwelling sample of elderly active Portuguese.

Methods

This cross-sectional study included 401 males and 401 females aged 60?C79?years old. Bone mineral density (BMD) of the total body, lumbar spine (LS), and hip region was determined by dual-energy X-ray absorptiometry (DXA). In addition, femur strength index (FSI) was determined. FF was assessed using the Senior Fitness Test. Demographic information and a health history were obtained by telephone interview through questionnaire.

Results

Aerobic endurance and body strength were positively related with hip BMD region in males (0.10?<?r?<?0.16; p?<?0.01?C0.05) and females (0.13?<?r?<?0.28; p?<?0.01). No significant correlation was found between any FF test and LS BMD, except for upper-body strength in females. After controlling for other constitutive predictors (sex, age, height, body mass (BM), total fat mass (TFM), and total lean tissue mass (TLTM)), FF had a minor contribution only in prediction of BMD at multisites and FSI. The total explained variance for all determinants was moderate (R2?=?0.35 for femoral neck (FN) BMD, R2?=?0.27 for LS BMD, R2?=?0.49 total body BMD, and R2?=?0.22 for FSI).

Conclusions

Sex, age, height, BM, TLTM, and TFM entered as the most significant contributors for BMD and FSI. Although FF parameters are typically considered in clinical assessments of bone health/strength in older people, body composition appears to have a higher relevance in the explanation of BMD and strength.     

Efficacy and safety of bazedoxifene in postmenopausal Asian women

Summary

This 6-month study examined the efficacy and safety of bazedoxifene 20?mg in postmenopausal Asian women. Bazedoxifene showed statistically significant improvements over placebo in bone mineral density at all skeletal sites evaluated. Bazedoxifene significantly reduced bone turnover and had favorable effects on lipid parameters. Bazedoxifene was safe and well tolerated.

Introduction

This 6-month, randomized, double-blind, placebo-controlled phase 3 study conducted in China, Korea, and Taiwan evaluated the efficacy and safety of bazedoxifene in postmenopausal Asian women.

Methods

Generally, healthy postmenopausal Asian women (N?=?487; mean age, 57.2?years; mean lumbar spine bone mineral density [BMD], ?1.1) were randomized to daily therapy with bazedoxifene 20?mg or placebo; all subjects received daily supplemental calcium carbonate 600?mg. The changes from baseline in BMD at the lumbar spine (primary end point) and at other skeletal sites, bone turnover markers, and lipid parameters were evaluated at 6?months. Safety assessments included adverse event (AE) reporting and physical/gynecologic examination.

Results

At 6?months, women who received bazedoxifene 20?mg had significantly greater BMD compared with those receiving placebo at the lumbar spine (0.41% vs ?0.32%, P?<?0.01), femoral neck (?0.08% vs ?0.69%, P?=?0.014), trochanter (0.50% vs ?0.23%, P?=?0.010), and total hip (?0.03% vs ?0.77%, P?<?0.001), respectively. Bazedoxifene 20?mg was also associated with significant differences from placebo in median percent reductions from baseline in serum C-telopeptide (?21.8%, P?<?0.001) and osteocalcin (?12.9%, P?<?0.001) levels and total (?5.0%, P?<?0.001) and low-density lipoprotein cholesterol (?9.5%, P?<?0.001) levels. The incidence of AEs was not different between subjects treated with bazedoxifene and those who received placebo.

Conclusion

Bazedoxifene was generally safe and effective in preventing bone loss in this short-term study of postmenopausal Asian women.