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.     

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.     

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.     

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.     

Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study

Summary

Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug.

Introduction

The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1–34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis.

Methods

Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N?=?65) or quarterly intravenous IBN (N?=?122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared.

Results

Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9?±?7.4 years, body mass index 23.8?±?3.8 kg/m², BMD L1–L4 0.741?±?0.100 g/cm², and TBS 1.208?±?0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 %?±?6.3 vs. +2.9 %?±?3.3 and +4.3 %?±?6.6 vs. +0.3 %?±?4.1, respectively; P?<?0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r ²?=?0.04) with no correlation between the changes in BMD and TBS over 24 months.

Conclusions

In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.     

Predictors of low bone mineral density of the stroke-affected hip among ambulatory individuals with chronic stroke

Summary

Risk of hip fracture is greater poststroke than in an age-matched healthy population, in part because of declining hip BMD. We found that individuals may be at risk of loss of hip BMD from muscle atrophy, asymmetrical gait, and poor affected-side ankle dorsiflexor strength. These impairments may be targeted during rehabilitation.

Introduction

This study aimed to determine predictors of low hip BMD on the stroke-affected side in people living in the community.

Methods

Forty-three participants (female; 27.9 %), mean age 62.4?±?13.5 and 17.9?±?32.8 months, poststroke with motor impairments underwent dual energy X-ray absorptiometry scans. Gait characteristics, isometric strength, body composition, and fasting plasma lipids were measured.

Results

At entry, 34.9 % (15/43) of the participants had low total hip BMD on the stroke-affected side. Of those with low BMD, 93.3 % (14/15) had a step length symmetry ratio >1, indicating greater reliance on the non-paretic leg for weight bearing. Logistic regression analysis revealed that lower affected-side ankle dorsiflexor strength (ß?=?0.700, p?=?0.02), lower total body fat-free mass index (ß?=?0.437, p?=?0.02), and greater step length symmetry ratio during walking (ß?=?1.135?×?10³, p?=?0.03) were predictors of low hip BMD.

Conclusion

Low BMD of the stroke-affected side hip is prevalent in over a third of individuals with lower limb motor impairments. These individuals may be at particular risk of accelerated loss of BMD at the hip from asymmetrical gait pattern and poor affected-side ankle dorsiflexor strength. These impairments are intervention targets that may be addressed during rehabilitation which includes resistance training and addresses gait impairments.     

Monitoring progress in the management of hip fractures in South Australia, Australia

Summary

The aim of this study was to assess trends in hip fracture rates and outcomes following hospitalisation for hip fracture. Hip fracture admissions increased over the study period. Men fared worst in terms of higher absolute mortality. Refracture rates and male health outcomes require further attention.

Purpose

The aim of this study was to assess trends in hip fracture rates and outcomes following hospitalisation for hip fracture in South Australia (SA).

Methods

Analysis of routinely collected, linked hospital separations data, of patients admitted to public and private hospitals in SA with a principal diagnosis of femoral neck fracture between July 2002 and June 2008 was done. Main outcome measures include number and rates of hospital admissions, 30-day in-hospital and 1-year mortality following a first hip fracture and subsequent event rates, by age and sex.

Results

Unadjusted hip fracture admissions increased in SA from 2002 to 2008 by 20?%, age-standardised (adjusted) admission rates increased overall (+5?%, p?=?0.215) and significantly amongst males (+26?%, p?=?0.001), while there was no change among women (?1?%, p?=?0.763). Within 1?year of a hip fracture, 7?% had broken another bone (5?% had refractured a hip). At 1?year post-fracture, unadjusted mortality was consistently and considerably higher amongst men compared to women (33 versus 19?%, p?<?0.001). Age-standardised mortality from admission to 1?year fell but not statistically significantly by 15?% in women (p?=?0.131) and 8?% in men (p?=?0.510). Women had a reduction in age-standardised in-hospital mortality over time (p?=?0.048); there was a non-significant decline in men (p?=?0.080).

Conclusions

Hip fracture admissions in SA increased over the study period and this appears to be driven by an increase in admissions amongst men. Men fared worst in terms of higher absolute mortality. There is some evidence to suggest refracture rates and male health outcomes require further attention.     

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.     

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.     

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.     

Sclerostin and Pref-1 have differential effects on bone mineral density and strength parameters in adolescent athletes compared with non-athletes

Summary

Excessive exercise can have detrimental effects on bone; however, the mechanisms leading to bone loss are not well understood. Sclerostin and preadipocyte factor (Pref)-1 are two hormones which inhibit bone formation. The present study demonstrates that these hormones may have differential effects in athletes as compared to non-athletes.

Introduction

Exercise activity is common in female adolescents, however, excessive exercise can have detrimental effects on bone mineral density (BMD). Mechanisms underlying this decrease in bone mass are not well understood. We investigated the effects of sclerostin, a potent inhibitor of bone formation via WNT signaling inhibition, and Pref-1, a suppressor of osteoblast differentiation, on BMD, bone turnover markers and bone strength in adolescent athletes.

Methods

We studied 50 adolescents between 15–21 years of age: 17 amenorrheic athletes (AA), 17 eumenorrheic athletes (EA), and 16 nonathletic controls (NA). We measured spine and hip BMD by dual energy x-ray absorptiometry and estimated failure load and stiffness at the distal radius and tibia using micro-finite element analysis. We also measured fasting sclerostin, Pref-1, N-terminal propeptide of type 1 procollagen, and C-terminal collagen cross-links levels.

Results

Sclerostin levels were higher in AA and EA compared with NA (AA: 0.42?±?0.15 ng/mL, EA: 0.44?±?0.09 ng/mL, NA: 0.33?±?0.14 ng/mL; p?=?0.047). In EA, sclerostin was positively associated with lumbar spine (LS) BMD and its Z-score (R?=?0.52, p?=?0.03 and R?=?0.55, p?=?0.02, respectively) whereas in NA, sclerostin was inversely associated with LS BMD (R?=??0.61, p?=?0.01). Pref-1 levels were similar in all three groups and there were significant inverse associations between Pref-1, BMD, and estimated bone strength in NA.

Conclusions

Sclerostin and Pref-1 may have differential effects on bone in adolescent athletes compared to non-athletes.     

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome

Summary

Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point.

Introduction

Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome.

Methods

VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry.

Results

Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3–17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2–15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), ?0.5?±?1.1; p?=?0.001) and at 3 months (?0.6?±?1.1; p?<?0.001), but not at 6 months (?0.3?±?1.3; p?=?0.066) or 12 months (?0.3?±?1.2; p?=?0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p?=?0.003). A subgroup (N?=?16; 25 %) had LS BMD Z-scores that were ≤?1.0 at 12 months. In these children, each additional 1,000 mg/m² of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, ?0.71 to ?0.07; p?=?0.017).

Conclusions

The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤?1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.     

Changes in Bone Mineral Density in Women Following 1-Year Gastric Bypass Surgery

Background

Roux-en-Y gastric bypass (RYGB) surgery is the gold standard surgical treatment for obesity. However, unintended nutritional deficiencies following this surgery are common, including changes in bone metabolism. We assessed changes in bone mineral density (BMD), nutritional compounds, and bone resorption markers before and 1?year following RYGB surgery.

Methods

Our study included 22 female patients with class II/III obesity. A clinical questionnaire, a 24-h recall, blood and urine samples, and dual-energy X-ray absorptiometry were provided.

Results

Mean age was 37.2?±?9.6?years; 86?% were Caucasian and 77.2?% were premenopausal. Mean preoperative body mass index was 44.4?±?5.0 and 27.5?±?4.5?kg/m² at 1-year follow-up (p?p?=?0.327]. Serum N-telopeptide (16.3?±?3.4 vs. 38.2?±?7.0 nM BCE, p?p?=?0.026) increased after RYGB surgery, reflecting bone resorption. BMD decreased after RYGB surgery in the lumbar spine (1.13?±?0.11 vs. 1.04?±?0.09?g/cm², p?=?0.001), femoral neck (1.03?±?0.15 vs. 0.94?±?0.16?g/cm², p?=?0.001), and total femur (1.07?±?0.11 vs. 0.97?±?0.15?g/cm², p?=?0.003).

Conclusions

Decreased BMD in the lumbar spine, femoral neck, and total femur is detectable in women 1?year after RYGB surgery. Calcium malabsorption, caused by vitamin D deficiency and increased bone resorption, is partially responsible for these outcomes and should be targeted in future clinical trials.     

Comparison of the effects of three oral bisphosphonate therapies on the peripheral skeleton in postmenopausal osteoporosis: the TRIO study

Summary

We compared the effects of oral alendronate, ibandronate and risedronate on the central and peripheral skeleton over 2 years. We report differences in effect on the central skeleton but not on the peripheral skeleton. Greater effects were observed for ibandronate (and alendronate) than risedronate at the spine but not the hip.

Introduction

Generally, comparative clinical trials of bisphosphonates have examined changes in bone within central skeletal regions. We have examined the effects of bisphosphonate treatment on the peripheral skeleton.

Methods

We conducted a 2-year, open-label, parallel randomised control trial of three orally administered bisphosphonates, at their licensed dose, to examine and compare their effects on the peripheral skeleton using multiple modes of measurement. We studied 172 postmenopausal women (53–84 years) who had either a bone mineral density (BMD) T-score of? ≤??2.5 at the spine and/or total hip or ?Premenopausal women (33–40 years, n?=?226) were studied to monitor device stability.

Results

We measured central BMD of the lumbar spine, total hip, total body and forearm using dual-energy X-ray absorptiometry. We measured calcaneus BMD (using dual-energy X-ray absorptiometry plus laser), radius and tibia BMD (using peripheral quantitative computed tomography), finger BMD (using radiographic absorptiometry), and phalangeal and calcaneal ultrasound variables (using quantitative ultrasound). Mixed effects regression models were used to evaluate effects of time and treatment allocation on BMD change. By 2 years, there were significant increases (p?Conclusions The increases in lumbar spine and total body BMD were greater with ibandronate and alendronate than with risedronate. Treatment effects on peripheral measurements did not differ between the three bisphosphonates.     

High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control

Summary

Fracture risk in type 1 diabetes (T1D) is supposed to be underestimated by bone mineral density (BMD). Individuals with T1D had more prevalent fractures in a cross-sectional study. Serum levels of pentosidine, an advanced glycation end product, and poor glycaemic control were associated with prevalent fractures independent of BMD.

Introduction

Type 1 diabetes (T1D) is associated with increased fracture risk. Bone mineral density (BMD) underestimates the risk of fractures in some individuals. The accumulation of advanced glycation end products (AGEs) impairs bone matrix and reduces bone strength.

Methods

In a cross-sectional study, 128 men and premenopausal women with T1D were evaluated. We compared traditional risk factors for fractures, BMD, parameters of bone metabolism and AGEs in individuals with and without prevalent fractures. An independent association of serum AGE levels with prevalent fractures was investigated.

Results

Individuals with prevalent fractures exhibited a longer duration of T1D, higher HbA1c and more diabetic-related complications. BMD at the femoral neck (z-score ?0.76?±?0.94 vs. ?0.23?±?1.02; p?=?0.031) and total hip (z-score ?0.54?±?0.93 vs. 0.11?±?1.11; p?=?0.017) was lower in those with prevalent fractures. Individuals with fractures had higher pentosidine levels (164.1?±?53.6 vs. 133.2?±?40.4; p?=?0.002). The levels of N-ε-(carboxymethyl)-lysine (CML) and endogenous secretory receptor for AGEs (esRAGE) did not significantly differ. Multivariate logistic regression analysis adjusted for age, BMI, family history of fractures, smoking, vitamin D deficiency, BMD at lumbar spine, femoral neck and total hip identified pentosidine levels and HbA1c as independent factors associated with prevalent fractures (odds ratio 1.02, 95 % CI 1.00–1.03/pmol/ml increase of pentosidine; p?=?0.008 and odds ratio 1.93, 95 % CI 1.16–3.20 per percentage increase of HbA1c; p?=?0.011).

Conclusions

The pentosidine levels but not BMD are independently associated with prevalent fractures. Impaired bone quality in T1D may result from increased AGE formation.     

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.     

The effects of adiponectin and leptin on changes in bone mineral density

Summary

We tested the hypothesis that low leptin and high adiponectin levels are associated with higher rates of bone mineral density (BMD) loss among 3,075 men and women, aged 70–79, from the Health Aging and Body Composition Study. Results suggest that adiponectin, but not leptin, is a risk factor for bone loss in women.

Introduction

Adiponectin and leptin are hormones secreted by adipose cells that may impact BMD. Few studies have evaluated the longitudinal association of leptin and adiponectin levels with rates of BMD change.

Methods

Hip and whole-body areal BMD (aBMD) were measured five times using dual-energy X-ray absorptiometry over 10?years (average follow-up time, 7.95 ± 1.92 years). Trabecular lumbar spine volumetric BMD (vBMD) was measured using quantitative computed topography at baseline and year?6 in the Pittsburgh cohort only. Random slope and intercept models were used to account for within person correlation as a result of repeated measures of hip and whole-body aBMD. Linear regression was used to model changes in spine trabecular vBMD.

Results

Among women, the annualized rate of hip aBMD loss in the highest tertile of adiponectin was ?0.67% (95% CI ?0.77, ?0.58) compared to [?0.43% (95% CI ?0.51, ?0.35)] in the lowest tertile (p trend?=?0.019) after adjusting for age, race, BMI, diabetes, baseline hip aBMD, and weight change. In men, hip aBMD loss was greatest in the high adiponectin group (tertile 3), however this association was not significant (p trend?=?0.148). After adjusting for weight change in women, the association between higher leptin and lower hip aBMD loss was attenuated and no longer significant (p trend?=?0.134). Leptin and adiponectin levels were not associated with whole-body aBMD or trabecular lumbar spine vBMD loss.

Conclusions

Adiponectin was associated with increased hip aBMD loss in women only, supporting evidence that adiponectin may have an important role in bone health.     

Effects of anti-resorptive agents on trabecular bone score (TBS) in older women

Summary

We evaluated the longitudinal effects of anti-resorptive agents (534 treated women vs. 1,150 untreated) on lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). TBS was responsive to treatment in women over age 50. The treatment-related increase in TBS was less than the increase in BMD, which is consistent with bone texture preservation.

Introduction

In addition to inducing an increase in BMD, anti-resorptive agents also help to preserve bone architecture. TBS, a new gray-level texture measurement, correlates with 3D parameters of bone micro-architecture independent of BMD. Our objective was to evaluate the longitudinal effects of anti-resorptive agents on lumbar spine BMD and TBS.

Methods

Women (≥50 years), from the BMD program database for the province of Manitoba, Canada, who had not received any anti-resorptive drug prior to their initial dual X-ray absorptiometry (DXA) exam were divided into two groups: untreated, those without any anti-resorptive drug over the course of follow-up, and treated, those with a non-estrogen anti-resorptive drug (86 % bisphosphonates, 10 % raloxifene, and 4 % calcitonin). Lumbar spine TBS was calculated for each lumbar spine DXA examination. Changes in TBS and BMD between baseline and follow-up (mean follow-up 3.7 years), expressed in percentage per year, were compared between the two groups.

Results

A total of 1,150 untreated women and 534 treated women met the inclusion criteria. Only a weak correlation was seen between BMD and TBS in either group. Significant intergroup differences in BMD change and TBS change were observed over the course of follow-up (p?<?0.001). Similar mean decreases in BMD and TBS (?0.36 %/year and ?0.31 %/year, respectively) were seen for untreated subjects (both p?<?0.001). Conversely, treated subjects exhibited a significant mean increase in BMD (+1.86 %/year, p?<?0.002) and TBS (+0.20 %/year, p?<?0.001).

Conclusion

TBS is responsive to treatment with non-estrogen anti-resorptive drug therapy in women over age 50. The treatment-related increase in TBS is less than the increase in BMD, which is consistent with bone texture preservation.     

The effects of weight loss approaches on bone mineral density in adults: a systematic review and meta-analysis of randomized controlled trials

Summary

We assessed the impact of weight loss strategies including calorie restriction and exercise training on BMD in adults using a systematic review of randomized controlled trials. Weight reduction results in reduced BMD at the hip, but has less effect on the spine. Both calorie restriction and a combination of calorie restriction and exercise result in a decrease in hip bone density, whereas weight loss response to exercise training without dietary restriction leads to increased hip BMD.

Introduction

Findings are not consistent on the effect of weight loss on bone mineral density (BMD). We conducted a systematic review on the randomized controlled trials to assess the effect of weight loss strategies, including calorie restriction and exercise programs on BMD in adults.

Methods

A structured and comprehensive search of MEDLINE and EMBASE databases was undertaken up to March 2016. Study-specific mean differences (MD) were pooled using a random-effects model. Subgroup analysis and meta-regression were used to find possible sources of between-study heterogeneity.

Results

Thirty-two randomized controlled trials met predetermined inclusion criteria. The meta-analysis revealed no significant difference on total BMD (MD 0.007, 95 % CI ?0.020–0.034, p?=?0.608). In contrast, the pooled data of studies showed a significant effect of weight loss on hip BMD (MD ?0.008, 95 % CI ?0.09 to ?0.006 g/cm², p?<?0.001) and also lumbar spine BMD (MD ?0.018 g/cm², 95 % CI ?0.019 to ?0.017, p?<?0.001). BMD in the hip site decreased after more than 4 months, especially in those who were obese. Moreover, calorie restriction interventions longer than 13 months showed a significant decreased in lumbar spine BMD.

Conclusion

Weight loss led to significant decreases at the hip and lumbar spine BMD but not at the total. Weight loss response following calorie restriction resulted in a decrease in hip and lumbar spine bone density especially more than 1 year; whereas an exercise-induced weight loss did not.