Role of APOE Gene in Bone Mineral Density and Incidence of Bone Fractures in Brazilian Postmenopausal Women

Osteoporosis is one of the major diseases that affects mostly postmenopausal women. Despite being a multifactorial disease, some genes have been shown to play an important role in osteoporosis. Bone mineral density (BMD) is still largely used to diagnose it, although many other biomarkers are used to better follow the disease onset. It has been shown that the apolipoprotein E (APOE) gene could be a biomarker for risk of fractures as well as to predict lower BMD in patients with osteoporosis. The human APOE gene encodes 3 protein isoforms called ApoE2, ApoE3, and ApoE4, resulting in 4 possible genotypes, because they are a product of a single nucleotide polymorphism found in this gene. So far, the APOE4 allele has been associated with low BMD in postmenopausal women and to incidence of bone breaking in older women. This study aimed to investigate the role of ApoE isoforms in a cohort of 413 postmenopausal Brazilian women. These patients were randomly recruited, clinically examined, and subjected to dual-energy X-ray absorptiometry to measure their BMD. Patients were further grouped as normal BMD (T-score?<?0.5) or low BMD (T-score?>?1.0, osteopenic or osteoporotic). Patients with osteopenia or osteoporosis were further genotyped for APOE alleles as well as tested for many serum bone turnover biomarkers. Our data showed that presence of the APOE3 allele was associated with both higher BMDs and higher serum concentrations of osteocalcin and alkaline phosphatase, biomarkers for bone formation. On the other hand, the APOE2 and APOE4 alleles were associated with lower BMD as well as higher levels of serum C-terminus collagen peptide and urinary deoxipyridinolines, biomarkers for bone resorption. However, these effects on lower BMD and bone resorption biomarkers observed in either APOE2 or APOE4 alleles were eliminated when patients' genotype carried the APOE3 allele. Codominance of the APOE3 allele was also associated with lesser cases of bone fractures in these patients within a 5-year follow-up. In conclusion, our data show that APOE4 may be associated with lower bone formation as well as increased risk of osteoporosis and bone fractures, whereas APOE3 seems to decrease lowering BMD in postmenopausal women, and its presence seemed to lower the incidence of bone breaking in patients with osteoporosis.     

Evidence that type I osteoporosis results from enhanced responsiveness of bone to estrogen deficiency

Type I osteoporosis occurs within 20 years after menopause and is associated with excessive cancellous bone loss and fractures of the vertebrae and distal radius. We have suggested that it may be caused by estrogen deficiency plus some additional factor predisposing to excessive bone loss. One such factor might be a greater degree of sex steroid deficiency, a possibility that could not be previously excluded because assays of sufficient sensitivity have only recently become available. Thus, we studied 36 women with vertebral fractures due to typical high turnover type I postmenopausal osteoporosis and 36 normal postmenopausal women using new ultrasensitive assays with detection limits of 1 pg/ml for estradiol, 5 pg/ml for estrone and 5 ng/dl for testosterone to test if type I osteoporosis results from enhanced responsiveness of bone to estrogen deficiency. Mean levels of serum sex steroids were identical in both groups, but bone turnover was increased by up to 55% in the women with type I osteoporosis. Moreover, compared with controls, the osteoporotic women had a 51% higher (P<0.01) serum osteoprotegerin level, which was likely a compensatory response to the increased bone turnover. In the osteoporotic women, 1-year treatment with transdermal estrogen in 14 women reduced total deoxypyridinoline, an index of bone resorption, by 58% as compared with placebo treatment in 17 women (P<0.001). Thus, as compared to controls, postmenopausal osteoporotic women had comparable sex steroid levels but higher bone turnover levels that were responsive to estrogen therapy. This is consistent with the hypothesis that the greater bone loss in type I osteoporosis is the result of impaired responsiveness of bone to low postmenopausal levels of sex steroids.     

Vitamin D status and bone turnover in women with acute hip fracture

Hypovitaminosis D is common in elderly women. Few data are available on vitamin D status and bone turnover in women with acute hip fracture. The aims of this study were to determine whether elderly Italian women with an acute hip fracture also had low vitamin D levels and an increase of bone turnover compared with elderly women with osteoporosis but without fractures. Seventy-four women with acute osteoporotic hip fracture and 73 women with postmenopausal osteoporosis were studied. All women were self-sufficient and had adequate sunlight exposure. To exclude the effect of trauma on serum 25-hydroxycolecalciferol levels and bone markers (bone alkaline phosphatase and C-terminal telopeptides of Type I collagen as indices of bone formation and bone resorption), blood samples were drawn within 24 hours of the fracture. Current data indicated that in our patients the prevalence of hypovitaminosis D is common although to a lesser extent than in women who are housebound. Women with acute hip fractures had a higher prevalence of vitamin deficiency defined as serum 25-hydroxycolecalciferol lower than 12 ng/mL, compared with women with osteoporosis. Moreover, the presence of fracture did not influence the rate of bone formation, whereas the increase in bone resorption could be attributed to an older age of women with acute hip fracture because of similar values of parathyroid hormone levels in the two groups.     

骨转换标志物在糖尿病中的研究进展

随着糖尿病和骨质疏松症在我国的广泛流行,糖尿病性骨质疏松症已成为糖尿病患者致死、致残的重要原因,严重影响患者的生活质量,并给个人、社会带来沉重负担。1型糖尿病患者骨密度降低,骨折风险增加;2型糖尿病患者骨密度常增高或正常,但骨折风险也是增加的,这不能仅靠双能X线骨密度来解释。骨转换标志物具有灵敏度高、特异性强、稳定性好等优点,近年来在糖尿病中得到广泛研究,如骨碱性磷酸酶、1型原胶原N-端前肽、1型胶原交联C-末端肽、骨钙素、骨保护素、脱氧吡啶啉等。骨转换标志物反映骨吸收和骨形成的具体变化情况,反映骨强度,较骨密度更早的反映骨量变化,大量临床研究发现,它为临床早期发现和诊断糖尿病性骨质疏松症,评估糖尿病患者骨折风险提供了新思路。联合检测骨转换标志物和骨密度,更全面、合理的评估骨转换,及时发现高危人群,更有利于糖尿病性骨质疏松症患者的早期诊断及治疗,预防骨折的发生。本文将对骨转换标志物在糖尿病中的研究进展作一综述。     

Biochemical markers of bone turnover for the clinical investigation of osteoporosis

The non-invasive assessment of bone turnover has received increasing attention over the past few years because of the need for sensitive markers in the clinical investigation of osteoporosis. Markers of bone formation include the serum measurement of total and bone-specific alkaline phosphatase, osteocalcin, and type I collagen extension peptides. Assessment of bone resorption can be achieved by measurement of urinary hydroxyproline, urinary excretion of the pyridinium crosslinks (pyridinoline and deoxypyridinoline), and by measurement of plasma tartrate-resistant acid phosphatase activity. For the screening of bone turnover in women at the menopause, and for the assessment of the level of bone turnover in elderly women with vertebral osteoporosis, serum osteocalcin and urinary pyridinoline appear to be the most sensitive markers, so far. Programs combining bone mass measurement and assessment of bone turnover by several markers in women at the time of menopause are being developed in an attempt to improve the assessment of the risk for osteoporosis. Efforts are made to develop more convenient assays and to identify other markers of bone turnover. In future a battery of various specific markers is likely to improve the assessment of the complex and subtle abnormalities of bone metabolism that characterize the various aspects of osteoporosis.     

Guidelines for the use of bone metabolic markers in the diagnosis and treatment of osteoporosis (2012 edition)

Recently the clinical application of bone metabolic markers has achieved significant progress and the measurements of these indices give us a better understanding of the pathogenesis of osteoporosis. Bone metabolic markers were adapted to select drug treatment for osteoporosis and to evaluate drug efficacy. Therefore, the proper application and assessment of bone metabolic markers in clinical practice is very important. To achieve these aims, the committee on the guidelines for the use of biochemical markers of bone turnover in osteoporosis authorized by the Japan Osteoporosis Society has summarized recent progress in bone markers and proposed the proper utilization of bone markers. Although the use of bone metabolic markers now has an important role in the daily management of osteoporosis, their use in Japan is still insufficient because of insurance coverage limitations. Since the Japan Osteoporosis Society first created the 2001 guidelines, new bone metabolic markers have been introduced into clinical practice. The availability of new osteoporosis treatments that promote bone formation has changed the clinical application of bone metabolic markers in current practice. Therefore, revisions to the current clinical practice are needed which led to the proposal to create these new 2012 guidelines.     

Clinical Use of Biochemical Markers of Bone Remodeling: Current Status and Future Directions

Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of bone mineral density (BMD). This review evaluates the use of commercially available bone turnover markers as aids in diagnosis and monitoring response to treatment in patients with osteoporosis. High within-person variability complicates but does not preclude their use. Elevated bone resorption markers appear to be associated with increased fracture risk in elderly women, but there is less evidence of a relationship between bone formation markers and fracture risk. The critical question of predicting fracture efficacy with treatment has not been answered. Changes in bone markers as currently determined do not predict BMD response to either bisphosphonates or hormone replacement therapy. Single measurements of markers do not predict BMD cross-sectionally (except possibly in the very elderly), or change in BMD in individual patients, either treated or untreated. On the other hand, research applications of bone turnover markers are of value in investigating the pathogenesis and treatment of bone diseases. Markers have potential in the clinical management of osteoporosis, but their use in this regard is not established. Additional studies with fracture endpoints and information on negative and positive predictive value are needed to evaluate fully the utility of bone turnover markers in individual patients.     

Potential for bone turnover markers to cost-effectively identify and select post-menopausal osteopenic women at high risk of fracture for bisphosphonate therapy

Introduction and hypothesis Over half of all fractures among post-menopausal women occur in those who do not have osteoporosis by bone density criteria. Measurement of bone turnover may cost-effectively identify a subset of women with T-score >−2.5 for whom anti-resorptive drug therapy is cost-effective. Methods Using a Markov model, we estimated the cost per quality adjusted life year (QALY) for five years of oral bisphosphonate compared to no drug therapy for osteopenic post-menopausal women aged 60 to 80 years with a high (top quartile) or low (bottom 3 quartiles) level of a bone turnover marker. Results For women with high bone turnover, the cost per QALY gained with alendronate compared to no drug therapy among women aged 70 years with T-scores of −2.0 or −1.5 were $58,000 and $80,000 (U.S. 2004 dollars), respectively. If bisphosphonates therapy also reduced the risk of non-vertebral fractures by 20% among osteopenic women with high bone turnover, then the costs per QALY gained were $34,000 and $50,000 for women age 70 with high bone turnover and T-scores of −2.0 and −1.5, respectively. Conclusion Measurement of bone turnover markers has the potential to identify a subset of post-menopausal women without osteoporosis by bone density criteria for whom bisphosphonate therapy to prevent fracture is cost-effective. The size of that subset highly depends on the assumed efficacy of bisphosphonates for fracture risk reduction among women with both a T-score >−2.5 and high bone turnover and the cost of bisphosphonate treatment.     

Intestinal hyperabsorption of calcium and low bone turnover in hypercalciuric postmenopausal osteoporosis

Hypercalciuria of intestinal origin has been linked with bone loss in calcium nephrolithiasis and idiopathic osteoporosis. This retrospective data analysis was performed to explore potential pathogenetic link between intestinal hyperabsorption of calcium and postmenopausal osteoporosis. Data were retrieved from postmenopausal women who were evaluated for osteoporosis or osteopenia at the Mineral Metabolism Clinic of UT Southwestern Medical Center. A total of 319 patients underwent the test of calciuric response to oral calcium load to obtain an indirect measure of intestinal calcium absorption. Serum and urinary biochemistry and L2–L4 bone mineral density (BMD) were compared between five quintiles of calciuric response. There was a statistically significant trend toward a rise in 24-h urinary calcium and a decrease in urinary deoxypyridinoline (DPD) and BMD, with increasing order of quintiles. The presentation of those in the 1st quintile was consistent with vitamin D insufficiency or deficiency, with impaired calcium absorption, secondary hyperparathyroidism, and stimulated bone turnover (high normal urinary DPD). In contrast, patients in the 5th quintile displayed a picture of absorptive hypercalciuria of stone disease, with intestinal hyperabsorption of calcium, high or high normal urinary calcium and suppressed bone turnover (low or low normal urinary DPD). Thus, the assessment of intestinal calcium absorption in a seemingly homogeneous group of postmenopausal women with osteoporosis or osteopenia revealed a spectrum of calciuric response whose extremes may represent two physiologically distinct subtypes that have important diagnostic and therapeutic implications.     

Low bone mineral density and high bone metabolism turnover in premenopausal women with unipolar depression

INTRODUCTION AND HYPOTHESIS: The majority of studies reporting decreased bone mineral density (BMD) in patients with unipolar depression neglected sex and age differences and menopause as the most important risk factor for osteoporosis. We presumed that physically healthy premenopausal women with unipolar depression have decreased BMD and altered bone cell metabolism. METHODS: BMD at lumbar spine and femoral neck by dual X-ray absorptiometry, bone alkaline phosphatase sera activity, 5b-tartarate resistant acid phosphatase sera activity and urine N-terminal telopeptide were measured in 73 premenopausal women with unipolar depression and compared with 47 healthy, age- and osteoporosis risk factors-matched premenopausal women. The duration and severity of depression, hormonal status (cortisol, prolactin, parathormone, oestradiol), antidepressive treatment, and physical activity through whole and modified QUALEFFO-41 questionnaire were evaluated. The results were statistically elaborated by the chi-square test, Student's t-test for independent samples, one-way analysis of variance - ANOVA, one-sample Kolmogorov-Smirnov test. Correlations were assessed by means of Pearson's coefficient. RESULTS: Patients with unipolar depression had significantly lower BMD, the decrease of which correlated only with the duration of depression. High bone metabolism turnover was found with a predomination of osteoresorption which, but not osteosynthesis, correlated with the severity of depression, estimated through Hamilton depression scores. Despite higher but not significant levels of cortisol in women with unipolar depression, the BMD decrease and high bone turnover seem not to be the consequence of hormonal changes or medical treatment. The significant correlations between physical activity and osteoresorption markers were found indicating possible underlying mechanism. CONCLUSIONS: Premenopausal women with unipolar depression have significantly lower BMD because of stimulated bone cell metabolism with predomination of osteoresorption process, mostly due to decreased physical activity in depression. These women should be investigated for osteoporosis and the multidisciplinary team approach is advocated.     

IL-33与绝经后骨质疏松女性骨密度和骨代谢指标相关性研究

目的 探索血清白细胞介素-33(IL-33)与绝经后骨质疏松女性骨密度和骨代谢指标相关性。方法 采用酶联免疫吸附法测定50例绝经后骨质疏松患者和50例正常绝经后妇女血清IL-33水平。采用双能X线骨密度仪(DXA)测量患者和对照组的骨密度(BMD)。检测维生素D、钙、碱性磷酸酶(ALP)、甲状旁腺激素(PTH)水平,以及1型胶原C末端肽(CTX)和1型前胶原N端前肽(P1NP)等骨转换指标。结果 在绝经后骨质疏松症女性中,IL-33水平显著低于健康对照组[(3.53±2.45) pg/mL vs (13.72±5.39) pg/mL,P=0.007];Spearman相关分析表明血清IL-33水平与年龄、BMI、PTH、CTX和P1NP水平呈负相关,与腰椎BMD和股骨颈BMD呈正相关。多元回归分析表明,年龄、BMI、腰椎BMD、PTH、股骨颈BMD和血清CTX和P1NP水平是骨质疏松症患者血清IL-33水平降低的独立预测因子。结论 血清IL-33降低是绝经后骨质疏松患者股骨颈和腰椎骨密度降低和骨转换增速的危险因素。     

Bone turnover markers: use in osteoporosis

Biochemical markers of bone turnover (bone turnover markers, BTMs) can be used to study changes in bone remodelling in osteoporosis. Investigators and clinicians should be aware of the appropriate sample collection and storage conditions for optimum measurements of these markers. Improvements in the variability of BTM measurements have resulted from the development of assays for automated analysers, and from international consensus regarding their use. Appropriate reference intervals should be used for the optimum interpretation of results. BTMs can provide information that is useful for the management of patients with osteoporosis, for both the initial clinical assessment and for guiding and monitoring of treatment. BTMs are clinically useful to determine possible causes of secondary osteoporosis by identifying patients with high bone turnover and rapid bone loss. In the follow-up of treatment response, BTM levels respond rapidly to both anabolic and antiresorptive treatments. BTM changes can also be used for understanding the mechanism of action of drugs in development and identifying the correct dose; they are also potentially useful as surrogate biomarkers for fracture.     

Effect of alendronate on bone mineral density and bone turnover markers in post-gastrectomy osteoporotic patients

Alendronate decreases the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX; about 45% at 3 months) and serum levels of alkaline phosphatase (ALP; about 27% at 24 months), leading to an increase in lumbar spine bone mineral density (BMD; about 9% at 24 months) in postmenopausal Japanese women with osteoporosis. However, the effectiveness of oral bisphosphonates on osteoporosis remains to be established in patients who have undergone a gastrectomy. The objective of the present case series study was to examine the effect of alendronate on BMD and bone turnover markers in post-gastrectomy osteoporotic patients. Sixteen patients (3 men and 13 postmenopausal women) with osteoporosis, who had undergone a gastrectomy (mean age: 69.1 years), were recruited in our outpatient clinic. All the patients were treated with alendronate (5 mg daily or 35 mg weekly) for 24 months. The effects of alendronate on lumbar spine (women) or total hip (men) BMD and urinary NTX and serum ALP levels were examined. A total or partial gastrectomy had been performed for eight patients each. The mean duration after surgery was 16.0 years. With alendronate therapy, urinary NTX levels significantly decreased at 3 months (−27.0%). Serum ALP levels decreased (−12.1%) and lumbar spine BMD increased (+5.2%), but total hip BMD did not significantly change (+0.6%) at 24 months. No severe adverse events were observed, and alendronate therapy was well tolerated. These results suggest that alendronate mildly increases lumbar spine BMD by mildly reducing bone turnover in osteoporotic patients after a gastrectomy.     

Biochemical assessment of bone turnover and bone fragility in men

SUMMARY: Osteoporosis in men is less studied than in women. Few data concern biochemical bone turnover markers (BTM) in men and their potential use. METHODOLOGY: We evaluated papers concerning BTM in men cited on Medline. Selection of studies were based on the number of subjects, age range, group homogeneity, follow-up duration, number of BTM. RESULTS: BTM levels are high in young men, then decrease with age.In elderly men, bone resorption increases with age more than bone formation. Variability of individual values is high and their significance is unclear. In elderly men, BTM levels correlate negatively with bone mineral density suggesting that accelerated bone turnover underlies age-related bone loss. Data on the prediction of accelerated bone loss and fractures by BTM in men are scant. Testosterone treatment induces a decrease in bone resorption followed by a decrease in bone formation. Bisphosphonates and calcitonin decrease BTM levels in osteoporotic men. Parathyroid hormone 1-34 and growth hormone induce a rapid increase in bone turnover followed by a progressive slowdown. CONCLUSIONS: Few studies concern BTM in men. Currently available data are not sufficient to suggest guidelines for the practical use of BTM in the clinical management of the osteoporosis in elderly men.     

Differential effects of teriparatide and alendronate on bone remodeling in postmenopausal women assessed by histomorphometric parameters.

An 18-month randomized double-blind study was conducted in postmenopausal women with osteoporosis to compare the effects of once-daily teriparatide 20 microg with alendronate 10 mg on bone histomorphometry. Biopsies were obtained from 42 patients. Indices of bone formation were significantly higher after 6 or 18 months of teriparatide compared with alendronate treatment. INTRODUCTION: Alendronate and teriparatide increased BMD, assessed by DXA, by different mechanisms of action, supported by changes in biochemical markers of bone turnover. The purpose of this cross-sectional study was to explore the differential effects of these two osteoporosis treatments at the bone tissue level by examining bone histomorphometric parameters of bone turnover after either 6 or 18 months of treatment. MATERIALS AND METHODS: Patients were a cohort from a randomized parallel double-blind study conducted to compare the effects of once-daily teriparatide 20 microg and alendronate 10 mg in postmenopausal women with osteoporosis. Transiliac crest bone biopsies were obtained after tetracycline double labeling from 42 patients treated for 6 months (n = 23) or 18 months (n = 14); 5 additional patients were biopsied from contralateral sides at 6 and 18 months. Biopsy specimens adequate for quantitative analysis were analyzed by 2D histomorphometry from 17 patients at 6 months (teriparatide, n = 8; alendronate, n = 9) and 15 patients at 18 months (teriparatide, n = 8; alendronate, n = 7). Data were analyzed by two-sample tests. RESULTS: Histomorphometric indices of bone formation were significantly and markedly greater in the teriparatide group than in the alendronate group at 6 and 18 months, whereas indices of bone resorption were only significantly greater in the teriparatide group than in the alendronate group at 6 months. Bone formation and activation frequency were significantly lower at 18 months compared with 6 months in the teriparatide group, returning to levels comparable with untreated postmenopausal women. In the teriparatide group, the peak in histomorphometric bone formation indices coincided with peak levels for N-terminal propeptide of type I collagen, a biochemical marker of bone formation. The degree of mineralization was lower at 18 months than at 6 months with treatment in both groups but was not different between groups. CONCLUSIONS: These results confirm the opposite mechanisms of action of teriparatide and alendronate on bone remodeling and confirm the bone formation effect of teriparatide.     

Long-term variability of markers of bone turnover in postmenopausal women and implications for their clinical use: the OFELY study.

Bone marker variability has raised concern for its use in individual patients. Serum osteocalcin (formation) and CTX (resorption) were measured every year for 4 years in 268 postmenopausal women. Seventy percent to 80% of women classified as having high bone turnover at baseline were similarly classified by the same methods 4 years later. INTRODUCTION: High bone marker levels are a risk factor for osteoporosis in postmenopausal women, but variability of measurements has raised doubts about their clinical use in an individual patient. METHODS: We studied 268 untreated postmenopausal women (50-81 years of age) belonging to a population-based prospective cohort. We collected fasting morning blood samples every year for 4 years to measure serum intact osteocalcin (OC) and serum C-terminal cross-linked telopeptide of type I collagen (CTX) as bone formation and resorption markers, respectively. RESULTS: Serum OC and CTX remained stable during follow-up (+ 1.2%/year, p = 0.003 and -0.13%/year, p = 0.70 for OC and S-CTX, respectively). At baseline, women were classified as having low (tertile 1), intermediate (tertile 2), or high (tertile 3) bone turnover. Agreement of classification between baseline and 4-year measurements was moderate (kappa [95% CI]: 0.51 [0.43-0.59] and 0.52 [0.44-0.60] for OC and S-CTX, respectively). Less than 10% of women in tertile 1 or 3 of either marker at baseline were found in the opposite tertile 4 years later. When the two markers were combined, only 2% of women at high turnover at baseline--defined as OC and/or S-CTX in tertile 3--were classified at low turnover 4 years later. Among women classified at high bone turnover at baseline (tertile 3), 70-80% were also found at high turnover 4 years later. Among women in tertile 2, only 51% and 43% for OC and CTX, respectively, remained in the same tertile at the second measurement. CONCLUSIONS: Serum levels of bone formation and resorption markers are stable over 4 years in postmenopausal women, on average. The majority of women classified as having high bone turnover were similarly classified by the same methods 4 years later. However, 20-30% of these women at risk for fracture would be incorrectly classified, suggesting that further investigation would be required to reduce the number of patients who would be treated unnecessarily if the decision was made on bone marker measurement. For women with intermediate levels, classification may be improved by a second measurement or by combining two markers.     

Prolonged bisphosphonate release after treatment in women with osteoporosis. Relationship with bone turnover

Bisphosphonates (BP), especially alendronate and risedronate, are the drugs most commonly used for osteoporosis treatment, being incorporated into the skeleton where they inhibit bone resorption and are thereafter slowly released during bone turnover. However, there are few data on the release of BP in patients who have received treatment with these drugs for osteoporosis. This information is essential for evaluating the possibility of BP cyclic therapy in these patients and for controlling their long-term presence in bone tissue. This study evaluated the urinary excretion of alendronate and risedronate in patients treated with these drugs for osteoporosis and analysed its relationship with bone turnover, time of previous drug exposure and time of treatment discontinuation. We included 43 women (aged 65 ± 9.4 years) previously treated with alendronate (36) or risedronate (7) during a mean of 51 ± 3 and 53 ± 3 months, respectively, who had not been treated with other antiosteoporotic treatment and with a median time of discontinuation of 13.5 and 14 months, respectively. Both BP were detected in 24-hour urine by HPLC. In addition, bone formation (PINP) and resorption (NTx) markers were analysed. Both BP were also determined in a control group of women during treatment. Alendronate was detected in 41% of women previously treated with this drug whereas no patient previously treated with risedronate showed detectable urinary values. All control patients showed detectable values of both BP. In patients with detectable alendronate levels, the time of drug cessation was shorter than in patients with undetectable values (12 [6–19] versus 31 [7–72] months, p < 0.001). Alendronate was not detected in any patient 19 months after treatment cessation. Alendronate levels were inversely related to time of treatment discontinuation (r = − 0.403, p = 0.01) and the latter was directly related to NTx (r = 0.394, p = 0.02). No relationship was observed with age, length of drug exposure, renal function or weight.In conclusion, contrary to risedronate, which was not detected in patients after cessation of treatment, alendronate was frequently detected in women previously treated with this agent up to 19 months after discontinuation of therapy. The relationship between alendronate levels and both bone resorption and time of treatment cessation further indicates a residual effect of this drug in bone, despite treatment discontinuation.     

Hormonal profiles and biochemical indices of bone turnover in Indian women

Summary The study establishes Indian referent database for bone turnover markers. The levels of markers decreased across the four quartiles of BMD showing a negative correlation with BMD. The study depicts that levels of hormones and bone turnover makers can aid in identifying women at risk for osteoporosis. Introduction Biochemical markers of bone turnover reflect changes in bone metabolism earlier and aid in the management of osteoporosis. Since a referent database for Indian women is lacking, the study was initiated to establish the same and suggest that hormonal profiles and markers of bone turnover can aid in identifying women at risk for osteoporosis. Methods Osteocalcin (OC), bone specific alkaline phosphatase ((BSAP), C-terminal crosslinking telopeptide of type-I collagen (CTX-I), deoxypyridinoline (DPD), follicle-stimulating hormone (FSH) and estrone glucuronide (E₁G) were measured in 365 Indian women (20–70 years) and correlated with BMD measurements by dual energy absorptiometry (DXA) using one way analysis of variance (ANOVA). Results The mean levels of bone resorption markers; CTX-I and DPD increased significantly across the age showing a negative correlation with BMD. The increase in levels of CTX-I and DPD was significantly higher (p < 0.0001) as compared to the femoral and spinal BMD, which dropped only 30–36%. The levels of bone turnover markers and FSH decreased across the four quartiles of spinal and femoral BMD showing a negative correlation whereas E₁G levels increased across the four quartiles. Conclusion The bone turnover markers were comparatively low in cohort of Indian women studied.     

Risk factors for decreased bone density and effects of HIV on bone in the elderly

SUMMARY: Most studies of bone density in HIV-infected individuals focus on young men. This study compares differences in bone density in elderly HIV positive men and women to HIV negative controls. Bone density was lower in the lumbar spine and hip in the HIV-infected group. Antiretrovirals may be associated with decreased bone mineralization. INTRODUCTION: Individuals with human immunodeficiency virus (HIV) may be at increased risk for osteoporosis. Prolonged exposures to HIV and/or antiretroviral therapy are possible causes for this association. This study compares differences in bone mineral density (BMD) in elderly HIV positive men and women to HIV negative controls. METHODS: A cross-sectional study was conducted among 57 HIV-infected and 47 HIV negative subjects over age 55. BMD at the lumbar spine and total hip and markers of bone turnover were compared. RESULTS: BMD was borderline lower in the lumbar spine and significantly lower in the hip in the HIV-infected group. Controlling for age, sex, race and body mass index, differences between the groups were significant at both sites. There was no difference in markers of bone turnover between the groups. Tenofovir use was significantly associated with decreased BMD at the spine while protease inhibitor use was significantly associated with decreased BMD at the hip. CONCLUSION: Elderly men and women with HIV have lower bone mass than HIV negative controls. Decreased body mass index was the most important risk factor associated with decreased BMD. Bone demineralization was observed among HIV-infected subjects receiving either tenofovir or a protease inhibitor.     

Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE study

Increasing evidence suggests that a high rate of bone turnover is associated with low bone mineral density (BMD) and is strongly linked to fracture risk. Measurement of biochemical markers of bone turnover is therefore becoming a more widely used endpoint in clinical trials in postmenopausal osteoporosis. This multinational double-blind, fracture-prevention study enrolled 2946 postmenopausal women with osteoporosis. Patients were randomized to receive placebo or oral ibandronate administered daily (2.5 mg/day) or intermittently (20 mg every other day for 12 doses every 3 months). The primary endpoint was the incidence of new vertebral fractures after 3 years. Secondary outcome measures included changes in the rate of bone turnover as assessed by biochemical markers and increases in spinal and hip BMD. Daily and intermittent oral ibandronate significantly reduced the risk of vertebral fractures by 62% and 50%, respectively, and produced significant and sustained reductions in all the measured biochemical markers of bone turnover. By 3 months, the rate of bone turnover was reduced by approximately 50–60%, and this level of suppression was sustained throughout the remainder of the study. In summary, oral ibandronate, given daily or with a between-dose interval of >2 months, normalizes the rate of bone turnover, provides significant increases in BMD and a marked reduction in the incidence of vertebral fractures. Thus, intermittent ibandronate has potential to become an important alternative to currently licensed bisphosphonates in postmenopausal osteoporosis.