Diabetic Polyneuropathy Relates to Bone Metabolism and Markers of Bone Turnover in Elderly Patients With Type 2 Diabetes: Greater Effects in Male Patients

BackgroundThere is evidence that diabetic polyneuropathy (PNP) is associated with reduced bone mineral density (BMD) in type 1 diabetes but little is known about the impact of diabetic PNP on bone metabolism in type 2 diabetes.ObjectivesThe aim of this study was to evaluate differences in bone metabolism by measuring markers of bone turnover and BMD in men and postmenopausal women with type 2 diabetes and diabetic PNP compared with those without PNP. Gender differences were analyzed for both groups of patients.MethodsOne hundred twenty patients with type 2 diabetes, 68 without PNP (43 men, 25 women, mean age 62 [8] years) and 52 with PNP (28 men, 24 women, mean age 64 [8] years) were studied. Clinical parameters with bone turnover biomarkers such as osteocalcin, bone alkaline phosphatase, procollagen type 1 amino-terminal propeptide, and carboxy-terminal telopeptide of type 1 collagen were measured in all patients. Dual energy x-ray absorptiometry to evaluate BMD was performed in a subgroup of patients.ResultsAfter controlling for age, body mass index, duration of diabetes, smoking, glycosylated hemoglobin, homeostasis model assessment index for insulin resistance, serum C-reactive protein, creatinine, calcium, gamma-glutamyltransferase, parathyroid and sex hormones levels, presence of micro/macrovascular complications, statin- as well as diabetes-related therapies, levels of carboxy-terminal telopeptide of type 1 collagen and procollagen type 1 amino-terminal propeptide were significantly higher among patients with PNP when compared with patients without PNP (P = 0.01 and P = 0.03, respectively). Differences in bone biomarkers were more pronounced among men with diabetes. BMD did not differ significantly between patients with and without PNP, independent of gender.ConclusionsMale patients with PNP exhibit a higher rate of bone turnover than men without PNP. High rate of bone turnover increases the susceptibility for developing osteoporosis. Prevention of diabetic PNP might also reduce the incidence of osteoporosis and fractures in patients with type 2 diabetes.     

Potassium Citrate Decreases Bone Resorption in Postmenopausal Women with Osteopenia: A Randomized,Double-Blind Clinical Trial

Objective: Diets rich in animal protein, such as the typical American diet, are thought to create a high acid load. An association between acid load and bone loss has led to the idea that providing positive alkaline salt therapy could have beneficial effects on bone metabolism. The objective of this study was to investigate the effects of potassium citrate (K-citrate), 40 mEq daily, over 1 year on bone resorption and formation.Methods: A randomized, double-blind, placebo-controlled trial of 83 women with postmenopausal osteopenia. Levels of bone turnover markers, specifically urinary N-telopeptide of collagen type 1 (u-NTX), amino-terminal propeptide of type 1 procollagen (P1NP), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC) were compared. Changes in bone mineral density (BMD) were also examined.Results: K-citrate decreased both u-NTX (P = .005) and serum P1NP (P<.001) starting at month 1 and continuing through month 12. No significant change was seen in BSAP or OC. No significant change was seen in lumbar or hip BMD between the 2 groups.Conclusion: In women with postmenopausal osteopenia, treatment with K-citrate for 1 year resulted in a significant decrease in markers of turnover. The effect on markers of bone formation was not consistent. K-citrate may serve as a potential treatment for bone loss that is well tolerated and without any significant known long-term consequences.Abbreviations:BMD = bone mineral densityBSAP = bone-specific alkaline phosphataseCa:Cr = calcium to creatinine ratioCTSC = Clinical Translational Science CenterCV = coefficient of variationDXA = dual-energy X-ray absorptiometryK-citrate = potassium citrateOC = osteocalcinP1NP = amino-terminal propeptide of type 1 procollagenu-NTX = urinary N-telopeptide of collagen type 1     

Bone Mineral Density,Bone Turnover Markers and Fractures in Patients with Systemic Sclerosis: A Case Control Study

Objective

The aim of our study was to elucidate the pathophysiology of systemic sclerosis-related osteoporosis and the prevalence of vertebral fragility fracture in postmenopausal women with systemic sclerosis (SSc).

Methodology

Fifty-four postmenopausal women with scleroderma and 54 postmenopausal controls matched for age, BMI, and smoking habits were studied. BMD was measured by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus The markers of bone turnover included serum osteocalcin and urinary deoxypyridinoline. All subjects had a spine X-ray to ascertain the presence of vertebral fractures.

Results

bone mineral density at lumbar spine (BMD 0.78±0.08 vs 0.88±0.07; p<0,001), femoral neck (BMD: 0.56±0.04 vs 0.72±0.07; p<0,001) and total femur (BMD: 0.57±0.04 vs 0.71±0.06; p<0,001) and ultrasound parameter at calcaneus (SI: 80.10±5.10 vs 94.80±6.10 p<0,001) were significantly lower in scleroderma compared with controls; bone turnover markers and parathyroid hormone level were significantly higher in scleroderma compared with controls, while serum of 25(OH)D3 was significantly lower. In scleroderma group the serum levels of 25(OH)D3 significantly correlated with PTH levels, BMD, stiffness index and bone turnover markers. One or more moderate or severe vertebral fractures were found in 13 patients with scleroderma, wherease in control group only one patient had a mild vertebral fracture.

Conclusion

Our data shows, for the first time, that vertebral fractures are frequent in subjects with scleroderma, and suggest that lower levels of 25(OH)D3 may play a role in the risk of osteoporosis and vertebral fractures.     

Osteocalcin: genetic and physical mapping of the human gene BGLAP and its potential role in postmenopausal osteoporosis.

Osteocalcin is an abundant, highly conserved bone-specific protein that is synthesized by osteoblasts. Temporally, osteocalcin appears in embryonic bone at the time of mineral deposition, where it binds to hydroxyapatite in a calcium-dependent manner. A role for osteocalcin in bone resorption has been suggested because of its ability to influence recruitment and differentiation of osteoclasts at the bone surface. The human osteocalcin gene has been mapped to 1q25-1q31 by somatic cell hybridization. In this paper, we refine both the genetic map and the physical map of osteocalcin and describe a new microsatellite (CA) marker, D1S3737, which is tightly linked to the gene. This marker and two other closely linked markers were used to identify alleles of the osteocalcin gene in case and control samples of postmenopausal white Iowans with low and high bone mineral density (BMD), respectively. A significant difference (P = 0.007) was observed between allele frequency distributions of case and control women with one of the markers, D1S3737. Further, logistic regression analysis determined one allele of D1S3737 as associated with BMD status in this population (P = 0.03). Our data suggest that genetic variation at the osteocalcin locus impacts BMD levels in the postmenopausal period and may predispose some women to osteoporosis.     

Long-Term Follow-up of patients on Drug Holiday from Bisphosphonates: Real-World Setting

ObjectiveAtypical femoral fractures and osteoporosis of the jaw have been associated with prolonged bisphosphonate therapy for postmenopausal osteoporosis. American Association of Clinical Endocrinologists guidelines suggest a drug holiday after 4 to 5 years of bisphosphonate treatment for moderate-risk patients and 10 years for high-risk patients, but there are minimal data on safe holiday durations. A recent U.S. Food and Drug Administration perspective suggests a treatment duration of 3 to 5 years. Our aim was to describe a group of patients on drug holiday and identify fracture risk.MethodsA retrospective chart review was conducted of 209 patients who started a bisphosphonate drug holiday between 2005 and 2010. Collected data included bone mineral density (BMD), markers of bone turnover, vitamin D status, and clinical and radiographic reports of fractures.ResultsEleven of 209 patients (5.2%) developed a fracture. Their mean age was 69.36 years (±15.58), and the mean lumbar spine and femoral neck T-scores were −2.225 (±1.779) and −2.137 (±0.950), respectively. All patients had a significant increase in bone-specific alkaline phosphatase at 6 months, which was more pronounced in the fracture group (3.0 ± 0.6083 μg/L vs. 1.16 ± 1.9267 μg/L). Over 4 years, there was no significant change in mean lumbar spine BMD for the entire cohort, but there was a statistically significant decline in the femoral neck BMD at year 2 (−0.0084 ± 0.03 gm/cm²).ConclusionThe current practice of initiating BP holidays needs further evaluation, particularly in the real-world setting. Elderly patients and those with very low BMD warrant close follow-up during a drug holiday. A fracture, early significant rise in bone turnover markers, and/or a decline in BMD should warrant resumption of osteoporosis therapy. (Endocr Pract. 2013;19:989-994)     

Prevention of Bone Loss After Withdrawal of Tamoxifen

ObjectiveTamoxifen has antiestrogenic effects in the breast and estrogenlike activity in the skeletons of post-menopausal women. We hypothesized that post-menopausal women with breast cancer would experience a rapid decline in bone mineral density (BMD) after stopping tamoxifen, similar to that seen with estrogen withdrawal. The objective of this study was to assess, in a randomized, double-blind, placebo-controlled trial, whether administration of alendronate (70 mg weekly) would prevent bone loss associated with tamoxifen discontinuation.MethodsPostmenopausal women with breast cancer were randomly assigned to receive alendronate or placebo for 1 year within 3 months after withdrawal of tamoxifen therapy. We initiated a randomized, double-blind, placebo-controlled trial of alendronate (70 mg weekly) in an effort to prevent bone loss associated with discontinuation of tamoxifen therapy. Patients treated with aromatase inhibitors were excluded from the study. BMD at the spine, hip, and forearm was measured at baseline and at 12 months. Analyses employed repeated-measures analysis of variance.ResultsPatient accrual was considerably limited by the substantial increase in use of aromatase inhibitors during the enrollment period. The study patients (N = 11) had similar baseline BMD T-scores in the alendronate (n = 6) and placebo (n = 5) subgroups. After 1 year, tamoxifen withdrawal was associated with a significant decline in BMD at the femoral neck, which appeared to be prevented by weekly administration of alendronate (-5.2% versus 0.1%; P = .02). Levels of urinary N-telopeptide, a marker of bone turnover, increased by 48% in study subjects in the placebo group (P < .01), whereas weekly alendronate treatment was associated with a 52% decline (P < .01) in this bone resorption marker.ConclusionDifferences in BMD and bone turnover were evident despite the small sample size. These data suggest that postmenopausal women with breast cancer completing tamoxifen therapy warrant an evaluation of their skeletal health and that bisphosphonate therapy may be useful in preventing bone loss associated with discontinuation of tamoxifen. (Endocr Pract. 2008;14:162-167)     

Bone Analysis Using Trabecular Bone Score and Dual-Energy X-Ray Absorptiometry-Based 3-Dimensional Modeling in Postmenopausal Women With Primary Hyperparathyroidism

ObjectivePredominance of bone loss in cortical sites with relative preservation of trabecular bone, even in postmenopausal women, has been described in primary hyperparathyroidism (PHPT). The aim of this study was to evaluate bone microarchitectural differences using dual-energy x-ray absorptiometry (DXA), trabecular bone score (TBS), and DXA-based 3-dimensional (3D) modeling (3D-DXA) between postmenopausal women diagnosed with PHPT (PM-PHPT) and healthy postmenopausal controls.MethodsThis retrospective study included 44 women with PM-PHPT (9 of whom had fractures) and 48 healthy women matched by age, body mass index, and years since menopause treated at Hospital Universitario Fundación Jiménez Díaz between 2008 and 2017. The bone mineral density (BMD) of the lumbar spine (LS), femoral neck, total hip (TH), and 1/3 radius was assessed using DXA, and trabecular volumetric BMD (vBMD), cortical vBMD, integral vBMD, cortical thickness, and cortical surface BMD at TH were assessed using a 3D-DXA software and TBS at LS.ResultsThe mean adjusted BMD values at LS, the femoral neck, and TH; TBS at LS; and TH 3D-DXA parameters (trabecular vBMD, integral vBMD, cortical thickness, and cortical surface BMD) were significantly reduced in women with PM-PHPT compared with those in the controls. However, differences in mean cortical vBMD were not statistically significant (P = .078). There were no significant differences in mean BMD, TBS, or the 3D-DXA parameters between patients with fractures and those without fractures. The 25-hydroxyvitamin D level appeared to be associated with TBS but not with DXA and 3D-DXA measurements.ConclusionPM-PHPT has significant involvement of the trabecular and cortical compartments of the bone, as determined by DXA, TBS, and 3D-DXA.     

Effect of Vitamin D Therapy on Bone Turnover Markers in Postmenopausal Women with Osteoporosis and Osteopenia

ObjectiveTo (7) assess the rate of reduction in bone turnover with vitamin D and bisphosphonate therapies and (2) evaluate the clinical utility of bone-specific alkaline phosphatase (BSAP) in monitoring treatment response.MethodsWe retrospectively reviewed medical records of patients with newly diagnosed osteopenia and osteoporosis from 2002 to 2009 at Loyola University Medical Center. A cohort of postmenopausal women with hip or spine T-scores of less than -1, normal serum creatinine, and no prior vitamin D or bisphosphonate therapy was divided into vitamin D-deficient (n = 29) and vitamin D-sufficient (n = 13) groups. Vitamin D-deficient patients received high-dose vitamin D, whereas vitamin D-sufficient patients received orally administered bisphosphonates. BSAP levels at baseline and 1 year were compared.Resultsvitamin D therapy in the group with vitamin D deficiency led to a 26.7% decrease in BSAP (P < .01). Bisphosphonate therapy in the vitamin D-sufficient group led to a 32.7% decrease in BSAP (P = .01). The magnitude of BSAP change in the 2 study groups (6.74 ± 6.48 μg ∕ L and 8.72 ± 9.94 μgZL) did not differ significantly (P = .45).ConclusionThe results of this study suggest that correction of vitamin D deficiency in patients with osteopenia and osteoporosis can lead to a decrease in bone turnover as measured by BSAP and that the magnitude of this reduction is similar to that achieved with orally administered bisphosphonates. (Endocr Pract. 2011;17:873-879)     

Alendronate Therapy in Men With Primary Hyperparathyroidism

ObjectiveTo determine the skeletal effects of alendronate therapy in men with primary hyperparathyroidism (PHPT) in comparison with those in postmenopausal women.MethodsThere essentially are no published data on the effects of bisphosphonate therapy in men with PHPT. We previously conducted a double-blind, randomized, single-crossover trial of alendronate, 10 mg daily, in PHPT and reported that alendronate significantly increases bone mineral density (BMD) at 12 months relative to baseline values. That study sample included both women (n = 28) and men (n = 9) and both premenopausal (n = 4) and postmenopausal (n = 24) women. Study subjects were randomly assigned to receive either alendronate or placebo during the first year, and all subjects received alendronate during the second year. Among the men, 3 received alendronate and 6 received placebo during the first year. The current analysis focuses on the skeletal effects of alendronate therapy in the 9 men during their first year of treatment versus the 6 men during their first year while receiving placebo as well as the 24 postmenopausal women during their first year of alendronate therapy. Paired t tests comparing baseline and 12-month data were performed for the 9 treated men and the 6 control subjects; unpaired t tests were used to compare the 9 treated men and the 24 treated women.ResultsAlendronate therapy for 1 year (n = 9) resulted in a 4.8% increase in BMD at the lumbar spine (P = .1) in comparison with the men who received 1 year of placebo (n = 6). Relative to baseline, men receiving alendronate showed a significant 4.4% gain in BMD at the lumbar spine (P = .009) and a 2.95% gain in total hip BMD (P = .027). A 47% decline in serum levels of bone-specific alkaline phosphatase activity was also noted with alendronate therapy (P = .003). Changes in BMD in the male population were similar to previously reported effects of alendronate therapy in postmenopausal women with PHPT.ConclusionAlendronate therapy in men with PHPT is associated with improvements in BMD and reductions in bone turnover. These data, similar to the findings in postmenopausal women with PHPT, suggest that aminobisphosphonates may be of value in providing skeletal protection for men with PHPT. Further study is needed to confirm skeletal protection and fracture efficacy in this population. (Endocr Pract. 2009;15:705-713)     

Bone Sparing Effect of a Novel Phytoestrogen Diarylheptanoid from Curcuma comosa Roxb. in Ovariectomized Rats

Phytoestrogens have been implicated in the prevention of bone loss in postmenopausal osteoporosis. Recently, an active phytoestrogen from Curcuma comosa Roxb, diarylheptanoid (DPHD), (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol, was found to strongly promote human osteoblast function in vitro. In the present study, we demonstrated the protective effect of DPHD on ovariectomy-induced bone loss (OVX) in adult female Sprague-Dawley rats with 17β-estradiol (E₂, 10 µg/kg Bw) as a positive control. Treatment of OVX animals with DPHD at 25, 50, and 100 mg/kg Bw for 12 weeks markedly increased bone mineral density (BMD) of tibial metaphysis as measured by peripheral Quantitative Computed Tomography (pQCT). Histomorphometric analysis of bone structure indicated that DPHD treatment retarded the ovariectomy-induced deterioration of bone microstructure. Ovariectomy resulted in a marked decrease in trabecular bone volume, number and thickness and these changes were inhibited by DPHD treatment, similar to that seen with E₂. Moreover, DPHD decreased markers of bone turnover, including osteocalcin and tartrate resistant acid phosphatase (TRAP) activity. These results suggest that DPHD has a bone sparing effect in ovariectomy-induced trabecular bone loss and prevents deterioration of bone microarchitecture by suppressing the rate of bone turnover. Therefore, DPHD appears to be a promising candidate for preserving bone mass and structure in the estrogen deficient women with a potential role in reducing postmenopausal osteoporosis.     

Prevalence of Osteoporosis in Ambulatory Postmenopausal Women from A Semiurban Region in Southern India: Relationship to Calcium Nutrition and Vitamin D Status

ObjectiveTo assess the prevalence of osteoporosis in healthy ambulatory postmenopausal Indian women as measured by dual-energy x-ray absorptiometry and to study the dietary calcium intake and vitamin D status and their influence on bone mineral density (BMD).MethodsWe conducted a community-based crosssectional study in a semiurban region. A randomized cluster sampling technique was used. The study cohort consisted of 150 ambulatory postmenopausal women (≥ 50 years old). Dual-energy x-ray absorptiometry for BMD was performed at the lumbar spine and femoral neck. Dietary calcium intake and biochemical variables were assessed.ResultsThe prevalence of osteoporosis was 48% at the lumbar spine, 16.7% at the femoral neck, and 50% at any site. The mean dietary calcium intake was much lower than the recommended intake for this age-group. There was a significant positive correlation between body mass index and BMD at the lumbar spine and the femoral neck (r = 0.4; P = .0001). BMD at the femoral neck was significantly less (mean, 0.657 versus 0.694 g/cm²) in the vitamin D-insufficient study subjects in comparison with the vitamin D-sufficient women (P = .03).ConclusionThe high prevalence of osteoporosis and vitamin D insufficiency in this semiurban group of postmenopausal women in India is a major health concern. Measures such as adequate calcium intake and vitamin D supplementation in women of this age-group may be beneficial. (Endocr Pract. 2008;14:665-671)     

绝经后骨质疏松症患者血清LECT2水平的临床意义及其预测价值分析

摘要 目的：探讨绝经后骨质疏松症患者血清白细胞衍生趋化因子2（LECT2）水平的临床意义及其预测价值。方法：选择2020年1月～2022年1月湖南师范大学第一附属医院收治的绝经后骨质疏松症患者125例作为研究组,另选取同期体检的绝经后健康女性志愿者120例作为对照组。比较两组血清LECT2水平,并分析血清LECT2水平与腰椎和股骨颈骨密度（BMD）及骨代谢相关指标的相关性;应用受试者工作特征（ROC）曲线分析血清LECT2对绝经后骨质疏松症患者的预测价值。结果：研究组血清LECT2、骨钙素（OC）、I型原胶原N端前肽（PINP）、 I型胶原交联C末端肽（S-CTX）显著高于对照组,腰椎和股骨颈BMD显著低于对照组（P<0.05）。Pearson相关分析显示,绝经后骨质疏松症患者血清LECT2水平与OC、PINP、S-CTX水平呈正相关（P<0.05）,与腰椎和股骨颈BMD呈负相关（P<0.05）。ROC曲线分析显示,血清LECT2、OC、PINP、S-CTX联合检验对绝经后骨质疏松症患者的预测价值的曲线下面积（AUC）为0.856,大于各单一指标预测。结论：绝经后骨质疏松症女性血清LECT2水平升高,其水平与骨代谢指标OC、PINP、S-CTX水平呈正相关,与腰椎BMD和股骨颈BMD呈负相关,血清LECT2联合OC、PINP、S-CTX对绝经后骨质疏松症患者的预测价值较高。     

Short-Term Oral Magnesium Supplementation Suppresses Bone Turnover in Postmenopausal Osteoporotic Women

Magnesium has been shown to increase bone mineral density when used in the treatment of osteoporosis, yet its mechanism of action is obscure. In this study, the effects of daily oral magnesium supplementation on biochemical markers of bone turnover were investigated. Twenty postmenopausal women have been divided into two groups. Ten patients were given magnesium citrate (1,830 mg/day) orally for 30 days. Ten postmenopausal women of matching age, menopause duration, and BMI were recruited as the control group and followed without any medication. Fasting blood and first-void urine samples were collected on days 0, 1, 5, 10, 20, and 30, respectively. Total magnesium, calcium, phosphorus, iPTH and osteocalcin were determined in blood samples. Deoxypyridinoline levels adjusted for creatinine were measured in urine samples. Thirty consecutive days of oral magnesium supplementation caused significantly decrease in serum iPTH levels in the Mg-supplemented group (p < 0.05). Serum osteocalcin levels were significantly increased (p < 0.001) and urinary deoxypyridinoline levels were decreased (p < 0.001) in the Mg-supplemented group. This study has demonstrated that oral magnesium supplementation in postmenopausal osteoporotic women suppresses bone turnover.     

Bone Mineral Density In Patients With Addison Disease On Replacement Therapy With Prednisolone

Objective: In primary adrenal insufficiency (PAI), replacement with prednisolone may result in lower bone mineral density (BMD) compared with hydrocortisone therapy. However, the number of patients studied on prednisolone is small and the results are conflicting. We conducted a cross-sectional study to determine BMD and its relation with therapy in patients on physiologic doses of prednisolone replacement.Methods: Forty-one consecutive patients (31 males, age &lsqb;mean ± SD] 50.9 ± 13.0 years), receiving prednisolone (hydrocortisone equivalent &lsqb;HCE] 13.0 ± 3.0 mg/m²) for 104 ± 95 months were studied. BMD was evaluated by dual-energy X-ray absorptiometry and compared with an age- and sex-matched reference group of healthy Indian subjects (n = 677).Results: Among males, BMD Z-scores (mean &lsqb;95% confidence interval {CI}]) at lumbar spine (-0.42 &lsqb;-0.80, -0.04]), femoral neck (-0.50 &lsqb;-0.95, -0.06]) and total hip (-0.58 &lsqb;-0.90, -0.26]) were significantly lower than the reference population. Z-scores in female patients did not differ from controls. Among postmenopausal females and males >50 years, 43% had osteoporosis (T-score ≤-2.5), as compared with 25% in the reference group (P = .04). There was no correlation between BMD Z-scores and HCE dose or duration of therapy. On multivariate regression analysis, body mass index was the only significant predictor of BMD. A high proportion of males (45%) had low serum testosterone (<300 ng/dL), but there was no correlation between testosterone and BMD.Conclusions: Male patients with PAI receiving physiologic prednisolone replacement had a small but significant diminution in BMD at all sites.Abbreviations:ACTH = adrenocorticotropic hormoneBAP = bone-specific alkaline phosphataseBMD = bone mineral densityBMI = body mass indexCI = confidence intervalHCE = hydrocortisone equivalent25 (OH) D3 = 25-hydroxyvitamin D3PAI = primary adrenal insufficiency     

No major effect of estrogen receptor beta gene RsaI polymorphism on bone mineral density and response to alendronate therapy in postmenopausal osteoporosis

Genetic factors play an important role in the pathogenesis of osteoporosis. The genes involved are, however, still largely unknown. In the present study, we have investigated whether sequence variations in the estrogen receptor beta (ERbeta) gene are associated with bone mineral density (BMD) and biochemical markers of bone turnover in 79 Slovenian postmenopausal women with osteoporosis. We also assessed the response by BMD and bone markers to antiresorptive therapy with bisphosphonate alendronate. All eight exons of ERbeta gene were amplified by polymerase chain reaction and screened for mutations by single-strand conformation polymorphism analysis. Potentially mutated samples were found only in exon 5 and sequence analysis identified the presence of a silent mutation in codon 328 with a nucleotide substitution GTG to GTA. For easier detection of this silent mutation, the RsaI restriction fragment length polymorphism analysis was developed. The frequencies of genotypes were as follows: Rr 5.1% and RR 94.9%. Between both genotypes, no significant differences in baseline lumbar spine and femoral neck BMD or in bone markers osteocalcin and deoxypyridinoline were observed. Similarly, no significant difference between RR and Rr genotypes in BMD or bone markers after 1 year of therapy was found. The increase in lumbar spine BMD after therapy was the only parameter that approached statistical significance (P=0.099). Patients with genotype Rr showed a smaller increase compared to those with RR. Our results suggest that RsaI polymorphism of ERbeta gene is probably not an important genetic determinant of BMD and does not significantly influence the responsiveness to alendronate therapy.     

Antiresorptive Agents Increase the Effects of Exercise on Preventing Postmenopausal Bone Loss in Women: A Meta-Analysis

Background and Objectives

It remains unknown whether the combination of antiresorptive agents and exercise would generate additive effects on bone mineral density (BMD) in postmenopausal women, though their separate roles in preventing bone loss have been well established. This meta-analysis aimed to evaluate the combined impact of antiresorptive treatment and exercise on the lumbar spine and femoral neck BMD in postmenopausal women compared with an exercise-only intervention.

Methods

A systematic literature search of PubMed, EMBASE, SportDiscus and ProQuest up to Jun 2014 was conducted to identify the influence of antiresorptive agents and exercise on BMD in postmenopausal women. The study quality of the included trials was evaluated. The effect sizes were estimated by calculating the standardized mean difference (SMD). Subgroup analyses were conducted by pharmacological regimens and exercise categories.

Results

Nine studies with a total of 1,248 postmenopausal women met the inclusion criteria. The heterogeneity between the studies was evident at the spine (I² = 78.7%) and hip (I² = 41.7%) measurements; random-effects models were used in the data analysis. The pooled effect sizes associated with the combined interventions of antiresorptive agents and exercise were significant at the lumbar spine BMD (SMD = 0.511, 95% CI = 0.118-0.904, p = 0.011). Combining hormone replacement therapy (HRT) and exercise training generated greater beneficial effects on lumbar spine (SMD = 0.729, 95% CI = 0.186-1.273, p = 0.009) and femoral neck BMD (SMD = 0.220, 95% CI = 0.0110-429, p = 0.039) than the exercise-only intervention. Impact exercise was sensitive to antiresorptive agents in preventing postmenopausal bone loss both at the spine (SMD = 1.252, 95%CI = 0.465-2.039, p = 0.002) and hips (SMD = 0.414, 95%CI = 0.106-0.723, p = 0.008).

Conclusions

Our findings indicate that antiresorptive agents significantly increase the impact of exercise on the prevention of bone loss in postmenopausal women, which implies that the combination of antiresorptive agents and exercise may generate additive effects.     

A Comparison of Bone Mineral Density and Its Predictors in HIV-Infected and HIV-Uninfected Older Men

ObjectiveBone health in older individuals with HIV infection has not been well studied. This study aimed to compare bone mineral density (BMD), trabecular bone score (TBS), and bone markers between HIV-infected men and age- and body mass index (BMI)-matched HIV-uninfected men aged ≥60 years. We investigated the associations of risk factors related to fracture with BMD, TBS, and bone markers in HIV-infected men.MethodsThis cross-sectional study included 45 HIV-infected men receiving antiretroviral therapy and 42 HIV-uninfected men. Medical history, BMD and TBS measurements, and laboratory tests related to bone health were assessed in all the participants. HIV-related factors known to be associated with bone loss were assessed in the HIV-infected men.ResultsThe mean BMD, TBS, and osteopenia or osteoporosis prevalence were similar among the cases and controls. The HIV-infected men had significantly higher mean N-terminal propeptide of type 1 procollagen and C-terminal cross-linking telopeptide of type I collagen levels. Stepwise multiple linear regression analysis demonstrated that low BMI (lumbar spine, P = .015; femoral neck, P = .018; and total hip, P = .005), high C-terminal cross-linking telopeptide of type I collagen concentration (total hip, P = .042; and TBS, P = .010), and low vitamin D supplementation (TBS, P = .035) were independently associated with low BMD and TBS.ConclusionIn older HIV-infected men with a low fracture risk, the mean BMD and TBS were similar to those of the age- and BMI-matched controls. The mean bone marker levels were higher in the HIV group. Traditional risk factors for fracture, including low BMI, high C-terminal cross-linking telopeptide of type I collagen level, and low vitamin D supplementation, were significant predictors of low BMD and TBS.     

Status of Bone Mineral Density in Patients Selected for Cardiac Transplantation

ObjectiveTo determine the prevalence and correlates of low bone mineral density (BMD) in ambulatory outpatients with end-stage heart failure who were awaiting cardiac transplantation.MethodsFifty-five cardiac transplant candidates with end-stage heart failure were enrolled in this study. Bone mineral density at the lumbar spine and proximal femur was determined by dual-energy x-ray absorptiometry. Laboratory studies included serum alkaline phosphatase, calcium, intact parathyroid hormone, and 25-hydroxyvitamin D.ResultsThe mean proximal femur and lumbar spine Z scores were 0.3 ± 1.1 and 0.3 ± 1.5, respectively. The mean BMD was not lower than that of the age- and sex- matched reference population. Z scores were less than -1 in 23% at the lumbar spine and 15% at the proximal femoral neck. On the basis of T scores, osteopenia (T scores between -1 and -2.5) was present in 24% (confidence interval, 13% to 35%) of patients at the lumbar spine and in 20% (confidence interval, 10% to 30%) at the proximal femur; osteoporosis (T scores of less than -2.5) was present in 4% of the study population. Half of the patients in this study sample had elevated intact parathyroid hormone levels, and a third of the patients had low 25-hydroxyvitamin D levels.ConclusionLumbar spine and hip BMD measurements were not significantly low relative to age and sex in ambulatory patients with heart failure awaiting cardiac transplantation. (Endocr Pract. 2008;14:704-712)     

Efectos del tratamiento con ácido zoledrónico en pacientes adultos con osteogénesis imperfecta

Background and objectiveOsteogenesis imperfecta (OI) is a genetic disorder that results in bone fragility. Several studies have demonstrated the effectiveness of bisphosphonate therapy. The aim of this study was to evaluate the effects of intravenous zoledronic acid on bone mineral density (BMD) and biochemical markers of bone turnover in adults with OI.Material and methodsWe carried out a prospective non-randomized study in patients with osteoporosis or severe osteopenia (T score <?2) related to OI and intolerance or contraindication to oral bisphosphonates. The patients were treated with a zoledronic acid infusion every 6 months. Densitometry was carried out annually. Calcium (Ca), phosphate (P), intact parathormone (PTH), 25 hydroxyvitamin D and biochemical markers of bone turnover [bone alkaline phosphatase (BAP), beta-cross-laps (CTX) and urinary deoxypyridoxine (DOP)] were measured every year. Adverse events and new fractures were registered.ResultsTen patients (2 men and 8 women) were treated. Treatment increased BMD measured in the lumbar spine after 24 (0.738±0.141 vs 0.788±0.144 g/cm²; p=0.048) and 36 months (0.720±0.139 vs 0.820±0.128; p=0.01). Significant increases in BMD were also observed after 24 months in the femoral neck (0.677±0.121 vs 0.703±0.122 g/cm²; p<0.016). Serum Ca, P, BAP and CTX concentrations remained unchanged. PTH concentrations increased and vitamin D concentrations decreased after 36 months of treatment. DOP excretion decreased significantly after 24 months. Seven patients had mild influenza-like symptoms occurring within the first 24 h after the first infusion. No severe adverse events were observed. None of the patients had new fractures.ConclusionZoledronic acid seems to be a safe and effective treatment option in adults with osteoporosis related to OI.     

Bone Mineral Density of the 1/3 Radius Refines Osteoporosis Diagnosis,Correlates With Prevalent Fractures,and Enhances Fracture Risk Estimates

ObjectiveTo investigate the added value of 1/3 radius (1/3R) for the diagnosis of osteoporosis by spine and hip sites and its correlation with prevalent fractures and predicted fracture risk.MethodsFracture Risk Assessment Tool (FRAX) scores for hip and major osteoporotic fractures (MOF) with/without trabecular bone score were considered proxy for fracture risk. The contribution of 1/3R to risk prediction was depicted via linear regression models with FRAX score as the dependent variable—first only with central and then with radius T-score as an additional covariate. Significance of change in the explained variance was compared by F-test.ResultsThe study included 1453 patients, 86% women, aged 66 ± 10 years. A total of 32% (n = 471) were osteoporotic by spine/hip and 8% (n = 115) by radius only, constituting a 24.4% increase in the number of subjects defined as osteoporotic (n = 586, 40%). Prior fracture prevalence was similar among patients with osteoporosis by spine/hip (17.4%) and radius only (19.1%) (P = .77).FRAX prediction by a regression model using spine/hip T-score yielded explained variance of 51.8% and 49.9% for MOF and 39.8% and 36.4% for hip (with/without trabecular bone score adjustment, respectively). The contribution of 1/3R was statistically significant (P < .001) and slightly increased the explained variance to 52.3% and 50.4% for MOF and 40.9% and 37.4% for hip, respectively.ConclusionReclassification of BMD results according to radius measurements results in higher diagnostic output. Prior fractures were equally prevalent among patients with radius-only and classic-site osteoporosis. FRAX tool performance slightly improved by incorporating radius BMD. Whether this approach may lead to a better fracture prediction warrants further prospective evaluation.