Predictive factors of change in BMD at 1 and 2 years in women with anorexia nervosa: a study of 146 cases

Summary

Bone mineral density (BMD; measured by DXA) changes were observed at all sites at 1?year in 146 patients with anorexia nervosa. Four independent factors accounted for the variation in BMD at the spine: duration of anorexia, bone-specific alkaline phosphatase (BAP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and triiodothyronine (T3). No change in BMD was observed from 1 to 2?years during follow-up.

Introduction

The purpose of this study was to assess changes in BMD at 1 and 2?years in anorexia nervosa patients, and to explore the relationships between change in BMD and various clinical and biological parameters measured at the first visit.

Methods

BMD was measured in anorexia nervosa patients at inclusion, at 1-year follow-up (n?=?146) and at 2-year follow-up (n?=?89).

Results

Bone loss was observed at all sites at 1?year. When multivariate analyses were performed, four independent factors accounted for the variation in BMD at the spine: duration of anorexia nervosa, BAP, ICTP, and T3. At the total hip site, leptin level was the main factor accounting for the variation in BMD. Strong correlations were also observed between weight at 1?year and change in BMD at 2?years. At the 2-year follow-up, no significant change in BMD was observed at the spine or femoral neck. In patients who were no longer amenorrheic at 1?year, a significant improvement in BMD at 2?years was observed at the total hip (+1.2%, p?=?0.02) and femoral neck (+3.7%, p?=?0.02). Similarly, in patients with a body mass index >17?kg/m² at 1?year, an improvement in BMD at the total hip at 2?years was observed (+3%, p?=?0.02)

Conclusion

Bone loss in anorexia nervosa patients occurs at an early stage, and the factors influencing such are different at the spine and hip.     

Differences in regional bone metabolism at the spine and hip: a quantitative study using 18F-fluoride positron emission tomography

Summary

This study showed that regional bone blood flow and ¹⁸F-fluoride bone plasma clearance measured by positron emission tomography are three times lower at the hip than the lumbar spine.

Introduction

Measurements of effective bone plasma flow (K ₁), bone plasma clearance (K _i ) and standardised uptake values (SUV) using ¹⁸F-fluoride positron emission tomography (¹⁸F-PET) provide a useful means of studying regional bone metabolism at different sites in the skeleton. This study compares the regional ¹⁸F-fluoride kinetics and SUV at the hip and lumbar spine (LS).

Methods

Twelve healthy postmenopausal women with no history of metabolic bone disease apart from two with untreated osteoporosis were recruited. Each subject underwent 60-min dynamic ¹⁸F-PET scans at the LS and proximal femur two weeks apart. K ₁, K _i and SUV were measured at the LS (mean of L₁–L₄), femoral neck (FN), total hip (TH) and femoral shaft (FS). Differences between sites were assessed using the nonparametric Kruskal–Wallis test with a Bonferroni correction for multiple comparisons.

Results

Values of K ₁, K _i and SUV at the FN, TH and FS were three times lower than at the LS (p?=?0.003). Amongst the proximal femur sites, K _i and SUV were lower at the FS compared with the FN and TH, and SUV was lower at the TH compared with the FN (all p?<?0.05). The volume of distribution was lower at the TH and FS compared with the LS (p?<?0.05).

Conclusion

The lower values of K ₁, K _i and SUV at the hip suggest that lower bone blood flow in the proximal femur is an important factor explaining the principal reason for the differences in bone fluoride kinetics between the LS and hip sites.     

Effect of alendronate in elderly patients after low trauma hip fracture repair

Summary

One year of once weekly alendronate, when given shortly after the surgical repair of a hip fracture, produces reductions in bone markers and increases proximal femoral bone density. The therapy was well tolerated.

Introduction

Hip fracture is the most devastating type of osteoporotic fracture and increases notably the risk of subsequent fractures. The aim of this paper was to evaluate the effects of 1 year therapy with a weekly dose of alendronate in the bone mineral density and bone markers in elderly patients after low trauma hip fracture repair.

Methods

Two hundred thirty-nine patients (81?±?7 years; 79.8% women) were randomized to be treated either with calcium (500 mg/daily) and vitamin D₃ (400 IU/daily; Ca–Vit D group) or with alendronate (ALN, 70 mg/week) plus calcium and vitamin D₃ (500 mg/daily and 400 IU/daily, respectively; ALN + Ca–Vit D group).

Results

One hundred forty-seven (61.5%) patients completed the trial. Alendronate increased proximal femoral bone mineral density (BMD) in the intention-to-treat analysis (mean difference (95% confidence interval); total hip 2.57% (0.67; 4.47); trochanteric 2.96% (0.71; 5.20), intertrochanteric 2.32% (0.36; 4.29)), but the differences were not significant in the BMD of the femoral neck (0.47%; (?2.03; 2.96) and the lumbar spine (0.69%; (?0.86; 2.23)). Bone turnover markers decreased during alendronate treatment.

Conclusion

The present study demonstrates for the first time the anti-resorptive efficacy of alendronate given immediately after surgical repair in an elderly population with recent hip fracture. This effect should positively affect the rate of subsequent fractures.     

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.     

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.     

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.     

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.     

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.     

Bone mineral density in men and children with haemophilia A and B: a systematic review and meta-analysis

Summary

Although haemophilia is not considered among the classic causes of secondary osteoporosis, the present meta-analysis provides strong evidence that men with haemophilia have a significant reduction in both lumbar spine and femoral bone mineral density, which appears to begin in childhood.

Introduction

Haemophilia is not considered among the classic causes of secondary osteoporosis. The aim of this study was to systematically review the literature for case–control trials that have studied bone mass in males with haemophilia and to meta-analyze the best evidence available.

Methods

Electronic databases MEDLINE, EMBASE and CENTRAL were systematically searched for case–control trials that have studied bone mass in men or boys with haemophilia. Standardized mean difference (SMD) for bone mineral density (BMD) in the lumbar spine was the main study outcome and SMD in femoral neck and total hip BMD the secondary ones. Patient and control characteristics, such as age, body mass index (BMI), level of physical activity and blood-borne infections were recorded as possible predictors of the main outcome.

Results

Thirteen studies were included in the systematic review and ten in the main outcome meta-analysis. Men with haemophilia demonstrated reduced lumbar spine [random effects SMD [95 % confidence interval (CI)] = ?0.56 (?0.84, ?0.28), between-study heterogeneity (I ²)?=?51 %] and femoral neck BMD [random effects SMD (95 % CI) = ?0.82 (?1.21, ?0.44), I ²?=?63 %] compared with controls, which indicated a large and clinically significant association. Similar results were obtained for children [random effects SMD (95 % CI) = ?0.92 (?1.77, ?0.07), I ²?=?92 %]. No evidence of publication bias was detected. There was no evidence that age, BMI, level of physical activity or presence of blood-borne infections predicted lumbar spine BMD.

Conclusions

This meta-analysis shows that men with haemophilia present a significant reduction in both lumbar spine and hip BMD, which appears to begin in childhood.     

Genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians

Summary

Osteoporotic fracture (OF) is a serious outcome of osteoporosis. Important risk factors for OF include reduced bone mineral density and unstable bone structure. This genome-wide copy number variation association study suggested VPS13B gene for osteoporosis in Caucasians.

Introduction

Bone mineral density (BMD) and femoral neck cross-sectional geometric parameters (FNCSGPs) are under strong genetic control. DNA copy number variation (CNV) is an important source of genetic diversity for human diseases. This study aims to identify CNVs associated with BMD and FNCSGPs.

Methods

Genome-wide CNV association analyses were conducted in 1,000 unrelated Caucasian subjects for BMD at the spine, hip, femoral neck, and for three FNCSGPs —cortical thickness (CT), cross-section area (CSA), and buckling ratio (BR). BMD was measured by dual energy X-ray absorptiometry (DEXA). CT, CSA, and BR were estimated using DEXA measurements. Affymetrix 500K arrays and copy number analysis tool was used to identify CNVs.

Results

A CNV in VPS13B gene was significantly associated with spine, hip and FN BMDs, and CT, CSA, and BR (p?<?0.05). Compared to subjects with two copies of the CNV, carriers of one copy had an average of 14.6%, 12.4%, and 13.6% higher spine, hip, and FN BMD, 20.0% thicker CT, 10.6% larger CSA, and 12.4% lower BR. Thus, a decrease of the CNV consistently produced stronger bone, thereby reducing osteoporotic fracture risk.

Conclusions

VPS13B gene, via affecting BMD and FNCSGPs, is a novel osteoporosis risk gene.     

The discriminatory capacity of BMD measurements by DXA and dual X-ray and laser (DXL) at the calcaneus including clinical risk factors for detecting patients with vertebral fractures

Summary

Osteoporotic fracture risk depends on bone mineral density (BMD) and clinical risk factors (CRF). Five hundred and eighty-eight untreated female and male outpatient subjects were evaluated, 160 with vertebral fractures. BMD was measured both by using calcaneal dual X-ray and laser (DXL) and dual-energy X-ray absorptiometry (DXA), and CRF were evaluated. Detection frequencies for different BMD methods with or without CRF are presented.

Introduction

Osteoporotic fracture risk depends on bone mineral density and clinical risk factors. DXA of the spine/hip is considered a gold standard for BMD assessment, but due to degenerative conditions, particularly among the older population, assessment of BMD at the lumbar spine has been shown to be of limited significance. Portable calcaneal dual X-ray technology and laser can be an easily obtainable alternative.

Methods

Vertebral fractures were evaluated in a baseline analysis of 588 females and males (median age 64.4, range 17.6–93.1 years), comparing BMD measurements by using DXL and DXA and CRF with/without BMD. One hundred and sixty subjects had radiological verified vertebral fractures. Area under receiver-operating characteristic curves (AUROCC) and univariate and multiple logistic regressions were calculated.

Results

AUROCC for detection of vertebral fractures was comparable for DXL at calcaneus and DXA at femoral neck (DXL 0.665 and DXA 0.670). Odds ratio for prevalent vertebral fracture was generally weak for DXA femoral neck (0.613) and DXL (0.521). Univariate logistic regression among CRF without BMD revealed age, prevalent fragility fracture, and body mass index significantly associated with prevalent vertebral fracture (AUROCC?=?0.805). Combining BMD and CRF, a prognostic improvement in case of DXA at femoral neck (AUROCC 0.869, p?=?0.02), DXL at calcaneus (AUROCC 0.869, p?=?0.059), and DXA at total hip (AUROCC 0.861, p?=?0.06) was observed.

Conclusions

DXL was similarly sensitive compared with DXA for identification of subjects with vertebral fragility fractures, and combination of CRF with BMD by DXL or DXA further increased the discriminatory capacity for detection of patients susceptible to vertebral fracture.     

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.     

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.     

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.     

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.     

A meta-analysis characterizing the dose–response relationships for three oral nitrogen-containing bisphosphonates in postmenopausal women

Summary

A meta-analysis of spine BMD dose–response relationships for alendronate, risedronate, and ibandronate was performed. Data from all three oral bisphosphonates conform to a log–linear relationship between dose and change in spine BMD relative to placebo at 1 year, with an incremental gain of about 1 % for each doubling of dose.

Introduction

Animal data suggesting differences in potency and differences in approved oral dosage strengths for alendronate, risedronate, and ibandronate in the treatment of osteoporosis raise questions about their dose–response relationships and relative potencies in humans.

Methods

A meta-analysis of dose–response relationships for spine BMD increases for these three bisphosphonates was performed using data from 21 placebo-controlled trials that collectively included over 13,000 patients on active treatment and over 8,000 on placebo.

Results

For alendronate over the range of 1 to 20 mg/day, there was a strong log–linear relationship between dose and the increase in spine BMD relative to placebo at 1 year (R ²?=?0.994 using sample-weighted means). For each doubling in alendronate dose, there was an incremental gain of about 1 % in spine BMD. On the same scale, risedronate and ibandronate are approximately equipotent to alendronate on a weight-for-weight basis. The increases in BMD efficacy with each doubling of dose are parallel for all three nitrogen-containing bisphosphonates (NCBPs).

Conclusions

All three NCBPs are approximately equipotent and exhibit a log–linear relationship between dose and the increase in spine BMD. Differences in efficacy between the available oral bisphosphonate regimens appear to be a function of dose rather than inherent differences in therapeutic potential.     

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.     

Zoledronic acid enhances bone-implant osseointegration more than alendronate and strontium ranelate in ovariectomized rats

Summary

This study was designed to compare the effects of alendronate (ALN), strontium ranelate (SR), and zoledronic acid (ZOL) on bone-implant osseointegration in ovariectomized rats. Histological examination and biomechanical tests show that ZOL, ALN, and SR enhance bone-implant osseointegration; ALN and SR have similar effects, while ZOL enhances bone-implant osseointegration more than ALN and SR

Introduction

This study aims to compare the effects of ALN, SR, and ZOL on bone-implant osseointegration in ovariectomized rats.

Methods

Sixty female Sprague–Dawley rats were included in this study. Of them, 48 rats were ovariectomized (OVX) and assigned to four groups: OVX (OVX?+?Veh), ALN (OVX?+?ALN), SR (OVX?+?SR), and ZOL (OVX?+?ZOL). And another 12 rats were sham-operated as a control group (Sham). Four weeks after ovariectomy, HA-coated titanium implants were inserted into the tibias bilaterally in all rats. Then the rats in groups ALN, SR, and ZOL were systemically administrated with alendronate (7 mg/kg/week, orally), strontium ranelate (500 mg/kg/day, orally), or a single injection of zoledronic acid (0.1 mg/kg, iv), respectively. Twelve weeks after implantation, all rats were sacrificed to get the femurs and tibias. Histological examination and biomechanical tests were used to evaluate bone-implant osseointegration in all groups.

Results

ALN, SR, and ZOL significantly increased distal femoral BMD when compared with group OVX; ZOL increased BMD significantly more than ALN and SR (P?<?0.05). Significant increase of bone-to-implant contact and peri-implant bone fraction were observed in groups ALN, SR, and ZOL when compared with group OVX (P?<?0.05). Groups ALN and SR were inferior to groups ZOL and Sham (P?<?0.05) in bone-to-implant contact and peri-implant bone fraction. Similar results were found in biomechanical testing (max pushout force).

Conclusions

In rats losing bone rapidly after ovariectomy, systemic administration of ZOL, ALN, and SR causes better bone-implant osseointegration when compared to OVX; ALN and SR have similar positive effects on osseointegration, while ZOL, that was given in a dose with more positive BMD effect than that of ALN or SR, causes better osseointegration than either ALN or SR.     

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.     

Exercise effects on hip bone mineral density in older, post-menopausal breast cancer survivors are age dependent

Summary

We evaluated whether age moderated the effect of impact + resistance exercise on hip BMD in older post-menopausal breast cancer survivors (BCS). Exercise was more beneficial among younger than older women within our sample, suggesting that much older BCS may require different training programs to improve hip health.

Purpose

Previously, we reported that a program of resistance + impact training stopped bone loss at the spine in older, post-menopausal BCS but had no effect on bone mineral density (BMD) at the hip. Aging may blunt the responsiveness of the hip to mechanical loading, so we conducted a secondary data analysis to evaluate whether age moderated the effect of exercise on hip BMD.

Methods

We analyzed data from our randomized, controlled trial in older (?? 50?years of age at diagnosis), post-menopausal, post-adjuvant treatment BCS (n?=?106) comparing women assigned to impact + resistance exercise (POWIR) or to a control program of low-intensity stretching (FLEX). We examined effect modification by age on BMD at three hip sites (greater trochanter, femoral neck, and total hip) using hierarchical linear modeling adjusting for time since diagnosis and use of adjuvant hormone therapy.

Results

Age moderated the effect of exercise on total hip BMD such that younger women in POWIR were more likely to see a positive net benefit than FLEX compared to older women where there was little difference between groups (p?=?0.02).

Conclusions

The skeletal response to loading at the hip within post-menopausal BCS diminishes with age. Whether more vigorous exercise programs and/or longer training periods are required to favorably change hip health in older BCS will require future study and careful thought about the risks and benefits of tougher training programs.