Accelerated Bone Loss Research Articles

C-telopeptide of type I collagen (CTX-1) in premenopausal Egyptian women with fibromyalgia syndrome

The majority of the fibromyalgia syndrome (FMS) patients do not exercise regularly and their physical fitness is low. Physical inactivity accelerates bone loss. This suggests that FMS patients are at risk in terms of osteoporosis. The aim of this study was to measure serum C-telopeptide of type I collagen (CTX-1) as a marker of bone resorption in premenopausal women with FMS. A total of 100 premenopausal female patients with FMS diagnosed according to the American College of Rheumatology (ACR) criteria 1990 and 50 healthy women were chosen to serve as the control group. Serum CTX-1 levels were measured using beta-CrossLaps Roche Elecsys. The serum CTX-1 level was significantly higher in patients with FMS compared with the control group. The mean serum CTX-1 in FMS patients was 340.2 ± 112.6 pg/ml compared with 283.6 ± 113.1 pg/ml in controls (P = 0.004). The serum CTX-1 level was positively correlated with the visual analogue scale(VAS) of pain (P = 0.028), the VAS of fatigue (P = 0.031), the VAS of global severity (P = 0.016), the VAS of anxiety (P = 0.013), the Health Assessment Questionnaire score (P = 0.022), the Fibromyalgia Impact Questionnaire (P = 0.010), the Beck Depression Inventory (P = 0.007), the tender points count (P = 0.003), the tender points score (P = 0.004), and the Pittsburg Sleep Quality Index (P = 0.021). The mean serum CTX-1 level was also significantly higher in FMS patients with postexertion pain (P = 0.010), confusion (P = 0.025), dizziness (P = 0.012), depression (P = 0.029), mood disturbance (P = 0.018), anxiety (P = 0.030), short memory difficulties (P = 0.017), and sleep disturbance (P = 0.028) than in those without these symptoms. We found a significant increase in serum CTX-1 in FMS patients compared with controls, and this was correlated with the disease severity. Increased CTX-1 may lead to the early development of osteoporosis. More comprehensive and detailed studies are needed to determine the exact role of CTX-1 in FMS.

The impact of diabetes and diabetes medications on bone health.

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures despite increased body weight and normal or higher bone mineral density. The mechanisms by which T2DM increases skeletal fragility are unclear. It is likely that a combination of factors, including a greater risk of falling, regional osteopenia, and impaired bone quality, contributes to the increased fracture risk. Drugs for the treatment of T2DM may also impact on the risk for fractures. For example, thiazolidinediones accelerate bone loss and increase the risk of fractures, particularly in older women. In contrast, metformin and sulfonylureas do not appear to have a negative effect on bone health and may, in fact, protect against fragility fracture. Animal models indicate a potential role for incretin hormones in bone metabolism, but there are only limited data on the impact of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 agonists on bone health in humans. Animal models also have demonstrated a role for amylin in bone metabolism, but clinical trials in patients with type 1 diabetes with an amylin analog (pramlintide) have not shown a significant impact on bone metabolism. The effects of insulin treatment on fracture risk are inconsistent with some studies showing an increased risk and others showing no effect. Finally, although there is limited information on the latest class of medications for the treatment of T2DM, the sodium-glucose co-transporter-2 inhibitors, these drugs do not seem to increase fracture risk. Because diabetes is an increasingly common chronic condition that can affect patients for many decades, further research into the effects of agents for the treatment of T2DM on bone metabolism is warranted. In this review, the physiological mechanisms and clinical impact of diabetes treatments on bone health and fracture risk in patients with T2DM are described.

Accelerated bone loss and increased post-fracture mortality in elderly women and men.

Bone loss, a fracture risk factor, may play a role in post-fracture mortality. We found accelerated bone loss (≥1.31 % bone loss/year for women and ≥1.35 % bone loss/year for men) associated with 44-77 % increased mortality. It remains unclear whether bone loss is a marker or plays a role in mortality. Osteoporotic fractures are associated with increased mortality although the cause is unknown. Bone loss, a risk factor for osteoporotic fracture is also associated with increased mortality, but its role in mortality risk post-fracture is unclear. This study aimed to examine post-fracture mortality risk according to levels of bone loss. Community-dwelling participants aged 60+ from Dubbo Osteoporosis Epidemiology Study with incident fractures were followed from 1989 to 2011. Kaplan-Meier survival curves were constructed according to bone loss quartiles. Cox proportional hazard models were used to determine the effect of bone loss on mortality. There were 341 women and 106 men with ≥2 BMD measurements. The rate of bone loss was similar for women and men (women mean -0.79 %/year, highest bone loss quartile -1.31 %/year; men mean -0.74 %/year, highest quartile -1.35 %/year). Survival was lowest for the highest quartile of bone loss for women (p < 0.005) and men (p = 0.05). When analysed by fracture type, the association of bone loss with mortality was observed for vertebral (highest vs lower 3 quartiles of bone loss, women p = 0.03 and men p = 0.02) and non-hip non-vertebral fractures in women (p < 0.0001). Bone loss did not play an additional role in mortality risk following hip fractures. Importantly, overall, rapid bone loss was associated with 44-77 % increased mortality risk after multiple variable adjustment. Rapid bone loss was an independent predictor of post-fracture mortality risk in both women and men. The association of bone loss and post-fracture mortality was predominantly observed following vertebral fracture in both women and men and non-hip non-vertebral fracture in women. It remains to be determined whether bone loss is a marker or plays a role in the mortality associated with fractures.

Current Options and Future Directions for Managing Osteoporosis: An update

Osteoporosis is considered as the most common metabolic bone disorder and characterized by low bone mass and skeletal fragility. Osteoporosis engages approximately about 200 millions of individuals, world widely. For instance, about 10 millions of Americans are affected and another 34 million are at risk of osteopenia [1]. Osteoporosis has been known as a silent disease. The affected patients do not often understand about the nature of their disease until it significantly develops so that the patients are often presented with osteoporosis related fractures [2]. Postmenopausal women are the most commonly affected population in the world and the fracture rates in postmenopausal Asian, American and African women have been reported to be 41, 54 and 91%, respectively [3]. During the postmenopausal period, the risk of fractures increases due to the accelerated bone loss because estrogen declines with age. Moreover, men are also affected by osteoporosis with the incidence of 20% [4]. Annually, $19 billion are accounted for osteoporotic fractures in health care expenditures which expected to rise to $25.3 billion in the future 10 years [5]. Each year, nearly 300,000 hip fractures, 547,000 vertebral fractures and almost 1,054,000 other fractures occur due to osteoporosis. Osteoporosis imposes more than 432,000 hospital admissions, 2.5 million medical office visits, and 180,000 nursing home admissions to the healthcare systems, annually [6]. Despite of several attempts, osteoporosis is still a considerable challenge for the governments.

Rodent models of osteoporosis.

The aim of this protocol is to provide a detailed description of male and female rodent models of osteoporosis. In addition to indications on the methods of performing the surgical procedures, the choice of reliable and safe anaesthetics is also described. Post-operative care, including analgesia administration for pain management, is also discussed. Ovariectomy in rodents is a procedure where ovaries are surgically excised. Hormonal changes resulting from ovary removal lead to an oestrogen-deprived state, which enhances bone remodelling, causes bone loss and increases bone fracture risk. Therefore, ovariectomy has been considered as the most common preclinical model for understanding the pathophysiology of menopause-associated events and for developing new treatment strategies for tackling post-menopausal osteoporosis. This protocol also provides a detailed description of orchidectomy, a model for androgen-deficient osteoporosis in rodents. Endocrine changes following testes removal lead to hypogonadism, which results in accelerated bone loss, increasing osteoporosis risk. Orchidectomised rodent models have been proposed to mimic male osteoporosis and therefore remain a valuable tool for understanding androgen deficiency in aged men. Although it would have been particularly difficult to assemble an internationally acceptable description of surgical procedures, here we have attempted to provide a comprehensive guide for best practice in performing ovariectomy and orchidectomy in laboratory rodents. Research scientists are reminded that they should follow their own institution's interpretation of such guidelines. Ultimately, however, all animal procedures must be overseen by the local Animal Welfare and Ethical Review Body and conducted under licences approved by a regulatory ethics committee.

Myelosuppressive therapies significantly increase pro-inflammatory cytokines and directly cause bone loss.

Skeletal-related events resulting from accelerated bone loss are common complications in patients treated for a range of cancers. However, the mechanisms and rate of bone loss after myelosuppression are unclear. We, therefore, investigated this in mice and humans. We treated mice with different myelosuppressive therapies (chemotherapy or irradiation with or without transplantation) and studied their effects on bone structure. Myelosuppression of mice rapidly caused an increase in bone resorption that was not matched by bone formation. The resultant significant and persistent bone loss early after therapy was associated with increased inflammatory cytokines, in particular, monocyte chemoattractant protein 1 (MCP1). Therapy-induced bone loss was prevented with a single dose of the bisphosphonate zoledronic acid (ZA), administered before myelosuppression. Importantly, ZA treatment of mice did not impair hematopoiesis, including hematopoietic stem cell function. Furthermore, examination of serum from patients before and after autologous or allogeneic stem cell transplantion (SCT) revealed altered levels of bone turnover markers and elevated inflammatory cytokines. MCP1 levels in serum obtained between days 7 and 14 post-SCT positively correlated with bone loss observed at 100 days after allogeneic SCT. Similar to that observed in our studies in mice, the bone loss was long term, persisting at 12 months post-SCT. Furthermore, patients who received chemotherapy less than 100 days before SCT had significantly more bone loss at the hip. In these patients, serum levels of MCP1, but not routine biomarkers of bone turnover, including C-terminal cross-linking telopeptide of type-1 collagen (β-CTx), positively correlated with their bone loss. Hence, myelosuppressive therapies increase inflammation and directly contribute to bone loss. Administration of an osteoclast inhibitor before the initiation of cancer therapy is likely to have the best outcome in preventing bone loss in patients with cancer.

Osteoporosis after renal transplantation

Bone loss and fracture are serious sequelae of kidney transplantation, associated with morbidity, mortality and high economic costs. The pathogenesis of post-transplantation bone loss is multifactorial and complex. Pre-existing bone mineral disease is responsible for a significant part, but it is aggravated by risk factors emerging after renal transplantation with immunosuppressive agents being one of the key contributors. The decrease in bone mass is particularly prominent during the first 6-12 months after transplantation, continuing at a lower rate thereafter. Bone mineral density measurements do not predict bone histology and bone biopsy findings reveal heterogeneous lesions, which vary according to time after transplantation. Currently, vitamin D and bisphosphonates are the most extensively tested therapeutic agents against this accelerated bone loss in renal transplant recipients. Both of these agents have proven effective, but there is no evidence that they decrease fracture risk. More studies are needed to examine the complex pathophysiologic mechanisms implicated in this population, as well as the effects of different therapeutic interventions on bone disorders after kidney transplantation.

Changes in bone mineral density at 3 years in postmenopausal women receiving anastrozole and risedronate in the IBIS-II bone substudy: an international, double-blind, randomised, placebo-controlled trial

Aromatase inhibitors prevent breast cancer in postmenopausal women at high risk of the disease but are associated with accelerated bone loss. We assessed effectiveness of oral risedronate for prevention of reduction in bone mineral density (BMD) after 3 years of follow-up in a subset of patients in the IBIS-II trial. The double-blind IBIS-II trial recruited 3864 healthy, postmenopausal women at increased risk of breast cancer and randomly allocated them oral anastrozole (1 mg/day) or matched placebo. 1410 (36%) postmenopausal women were then enrolled in a bone substudy and stratified at baseline according to their lowest baseline T score at spine or femoral neck (stratum I: T score at least -1·0; stratum II: T score at least -2·5 but less than -1·0; stratum III: T score less than -2·5 but greater than -4·0). Women in stratum I were monitored only; women in stratum III were all given risedronate (35 mg/week). Women in stratum II were randomly assigned (1:1) to risedronate (35 mg/week) or matched placebo by use of a block randomisation schedule via a web-based programme. The primary outcome of this per-protocol analysis (done with all women with a baseline and 3 year DXA assessment) was the effect of risedronate versus placebo for osteopenic women in stratum II randomly allocated to anastrozole (1 mg/day). Secondary outcomes included effect of anastrozole (1 mg/day) on BMD in women not receiving risedronate (strata I and II) and in osteoporotic women who were all treated with risedronate (stratum III). The trial is ongoing, but no longer recruiting. This trial is registered, number ISRCTN31488319. Between Feb 2, 2003, and Sept 30, 2010, 150 (58%) of 260 women in stratum II who had been randomly allocated to anastrozole and either risedronate or placebo had baseline and 3 year assessments. At the lumbar spine, 3 year mean BMD change for the 77 women receiving anastrozole/risedronate was 1·1% (95% CI 0·2 to 2·1) versus -2·6% (-4·0 to -1·3) for the 73 women receiving anastrozole/placebo (p<0·0001). For the total hip, 3 year mean BMD change for women receiving anastrozole/risedronate was -0·7% (-1·6 to 0·2) versus -3·5% (-4·6 to -2·3) for women receiving anastrozole/placebo (p=0·0001). 652 (65%) of 1008 women in strata I and II who were not randomly allocated to risedronate had both baseline and 3 year assessments. Women not receiving risedronate in stratum I and II who received anastrozole (310 women) had a significant BMD decrease after 3 years of follow-up compared with women who received placebo (342 women) at the lumbar spine (-4·0% [-4·5 to -3·4] vs -1·2% [-1·7 to -0·7], p<0·0001) and total hip (-4·0% [-4·4 to -3·6] vs -1·8% [-2·1 to -1·4], p<0·0001). 106 (79%) of 149 women in stratum III had a baseline and a 3 year assessment. The 46 women allocated to anastrozole had a modest BMD increase of 1·2% (-0·1 to 2·6) at the spine compared with a 3·9% (2·6 to 5·2) increase for the 60 women allocated to placebo (p=0·006). For the total hip, a small 0·3% (-0·9 to 1·5) increase was noted for women allocated anastrozole compared with a 1·5% (0·5 to 2·5) increase for women allocated placebo, but the difference was not significant (p=0·12). The most common adverse event reported was arthralgia (stratum I: 94 placebo and 114 anastrozole; stratum II: 39 placebo/placebo, 25 placebo/risedronate, 34 anastrozole/placebo, and 34 anastrozole/risedronate; stratum III: 21 placebo/risedronate, 17 anastrozole/risedronate). Other adverse events included hot flushes, alopecia, abdominal pain, and back pain. Risedronate counterbalances the effect of anastrozole-induced bone loss in osteopenic and osteoporotic women and might be offered in combination with anastrozole treatment to provide an improved risk-benefit profile. Cancer Research UK (C569/A5032), National Health and Medical Research Council Australia (GNT300755, GNT569213), Sanofi-Aventis, and AstraZeneca.

The effects of thyrotropin-suppressing therapy on bone metabolism in patients with well-differentiated thyroid carcinoma

Studies on the effects of levothyroxine (LT4) therapy on bone and bone metabolism have yielded conflicting results. This 1-year prospective study examined whether LT4 in patients with well-differentiated thyroid carcinoma (DTC) is a risk factor for bone mass loss and the subsequent development of osteoporosis.We examined 93 patients with DTC over 12months after initiating LT4 therapy (early postoperative period). We examined another 33 patients on long-term LT4 therapy for DTC (late postoperative period). Dual energy X-ray absorptiometry was performed at baseline and after 1year.The mean bone losses during the early postoperative period in the lumbar spine, femoral neck, and total hip, calculated as the percentage change between levels at baseline and 12months, were −0.88, −1.3 and −0.81%, respectively. Bone loss was more evident in postmenopausal women (lumbar spine −2.1%, femoral neck −2.2%, and hip −2.1%; all P<0.05). We compared the changes in annual bone mineral density (BMD) in postmenopausal women according to calcium/vitamin D supplementation. Bone loss tended to be higher in the postmenopausal women receiving no supplementation. There was no decrease in BMD among patients during the late postoperative period. The mean bone loss was generally greater in the early than in the late postoperative group, and this was significant at the lumbar spine (P=0.041) and femoral neck (P=0.010).TSH-suppressive levothyroxine therapy accelerates bone loss, predominantly in postmenopausal women and exclusively during the early post-thyroidectomy period.

Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice.

Iron overload accelerates bone loss in mice lacking the bone morphogenetic protein 6 (Bmp6) gene, which is the key endogenous regulator of hepcidin, iron homeostasis gene. We investigated involvement of other BMPs in preventing haemochromatosis and subsequent osteopenia in Bmp6-/- mice. Iron-treated wild-type (WT) and Bmp6-/- mice were analysed for hepcidin messenger RNA (mRNA) and tissue and blood BMP levels by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), immunohistochemistry, Western blot, enzyme-linked immunosorbent assay (ELISA) and proximity extension assay. BMPs labeled with technetium-99m were used in pharmacokinetic studies. In WT mice, 4h following iron challenge, liver Bmp6 and hepcidin expression were increased, while expression of other Bmps was not affected. In parallel, we provided the first evidence that BMP6 circulates in WT mice and that iron increased the BMP6 serum level and the specific liver uptake of (99m)Tc-BMP6. In Bmp6-/- mice, iron challenge led to blunted activation of liver Smad signaling and hepcidin expression with a delay of 24h, associated with increased Bmp5 and Bmp7 expression and increased Bmp2, 4, 5 and 9 expression in the duodenum. Liver Bmp7 expression and increased circulating BMP9 eventually contributed to the late hepcidin response. This was further supported by exogenous BMP7 therapy resulting in an effective hepcidin expression followed by a rapid normalisation of plasma iron values and restored osteopenia in Bmp6-/- mice. In Bmp6-/- mice, iron activated endogenous compensatory mechanisms of other BMPs that were not sufficient for preventing hemochromatosis and bone loss. Administration of exogenous BMP7 was effective in correcting the plasma iron level and bone loss, indicating that BMP6 is an essential but not exclusive in vivo regulator of iron homeostasis.

Tibia bone properties at different time course of ovariectomized rats.

BackgroundThe model of bilaterally ovariectomized rats mimics the accelerated bone loss observed in postmenopausal women due to estrogen deficiency. Although calcium is main mineral in bone, previous study in human showed there is hypermineralization and higher calcium level in hydroxyapatite crystal structure from osteoporosis patients. This study was aimed to investigate the effect of time course ovariectomized on tibia bone turn over markers, mineral elements, hydroxyapatite crystale, mesostructure, and histomorphometry.MethodsA total of 30 Wistar female rats were randomly assigned into three groups (n = 10 each): control group, ovariectomy group follow up for one month and two month. All animals procedures was according to Animal Ethics Guidelines and approval by ethic committee of the Medical Faculty, Lambung Mangkurat University which obtained prior the study. Expression of osteocalcin (OC) and C-telopeptyde collagen type I (CTX) was analyzed by ELISA method. Tibia bone mineral element was measured using X-Ray Fluorescence. Hydroxyapatite crystale structure was analyzed using X-Ray Diffracttion. Mesostructure was determined using Scanning Electron Microscope. Histomorphometry was analyzed using BoneJ software analyzer. ANOVA test was used to analyze the different level of serum bone turnover markers and bone mineral elements.ResultsSerum OC and CTX were significantly decrease in one month and two month after ovariectomized groups compared to sham-operated group (P < 0.05). The levels Ca, P, Fe, Cu, Zn, Ni, Ca/P, and Cu/Zn were not significantly different in all groups (P > 0.05). The structure of hydroxyapatite crystal in one month and two month after ovariectomized groups were different compared with sham-operated control group. Mesostructure of tibia bone after one and two month ovariectomized procedure significantly different than that in sham-operated rats. The level of trabecular volume were lower significantly on OVX-1 and OVX-2 groups compared with sham group (P < 0.05). The trabecular thickness and spacing were increase significantly on OVX-1 and OVX-2 groups compared with sham group (P < 0.05). The trabecular number were significantly decrease OVX-1 and OVX-2 groups than that sham group (P < 0.05).ConclusionWe found that two month after ovariectomized decrease serum osteocalcin but not change bone mineral elements in rats. Also, we found the difference of lattice parameter of hydroxyapatite crystale structure and trabecular properties which determined bone mesostructure.

Bone health in cancer patients: ESMO Clinical Practice Guidelines

There are three distinct areas of cancer management that make bone health in cancer patients of increasing clinical importance. First, bone metastases are common in many solid tumours, notably those arising from the breast, prostate and lung, as well as multiple myeloma, and may cause major morbidity including fractures, severe pain, nerve compression and hypercalcaemia. Through optimum multidisciplinary management of patients with bone metastases, including the use of bone-targeted treatments such as potent bisphosphonates or denosumab, it has been possible to transform the course of advanced cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life. Secondly, many of the treatments we use to treat cancer patients have effects on reproductive hormones, which are critical for the maintenance of normal bone remodelling. This endocrine disturbance results in accelerated bone loss and an increased risk of osteoporosis and fractures that can have a significant negative impact on the lives of the rapidly expanding number of long-term cancer survivors. Finally, the bone marrow micro-environment is also intimately involved in the metastatic processes required for cancer dissemination, and there are emerging data showing that, at least in some clinical situations, the use of bone-targeted treatments can reduce metastasis to bone and has potential impact on patient survival.

Bone density is normal and does not change over 2years in sarcoidosis.

Small studies have previously suggested that sarcoidosis may be associated with low bone mineral density. In this observational study of 64 patients with sarcoidosis, bone mineral density was within the normal range at baseline, and there was no evidence of accelerated bone loss over 1-2 years. Several small studies have suggested that sarcoidosis may be associated with low bone mineral density (BMD). We undertook a cross-sectional study of BMD in 64 patients with sarcoidosis. Of these, 27 with 25-hydroxyvitamin D<50 nmol/L entered a 1-year intervention study of vitamin D supplements, and 37 entered a 2-year longitudinal study of BMD, with the primary endpoint of the change in lumbar spine BMD. The mean age of participants was 58 years, 68% were female, and 8% were currently using oral glucocorticoids. At baseline, BMD for the entire cohort was greater than the expected values for the population at the lumbar spine (mean Z-score 0.7, P<0.001) and total body (0.5, P<0.001) and similar to expected values at the femoral neck (0.2, P=0.14) and total hip (0.2, P=0.14). BMD did not change at any of these four sites (P>0.19) over 2 years in the longitudinal study. In the intervention study, vitamin D supplements had no effect on BMD, and therefore we pooled the data from all participants. BMD did not change over 1 year at the spine, total hip, or femoral neck (P>0.3), but decreased by 0.7% (95% confidence interval 0.3-1.1) at the total body (P=0.019). BMD was normal at baseline, and there was no consistent evidence of accelerated bone loss over 1-2 years, regardless of baseline vitamin D status. Patients with sarcoidosis not using oral glucocorticoids do not need routine monitoring of BMD.

Association of stressful life events with accelerated bone loss in older men: the osteoporotic fractures in men (MrOS) study.

Prior studies suggest an association between stressful life events and fractures that may be mediated by BMD. In the current study, risk of accelerated hip BMD loss was higher in older men with any type of stressful life event and increased with the number of types of stressful life events. Prior studies suggest that stressful life events may increase adverse health outcomes, including falls and possibly fractures. The current study builds on these findings and examines whether stressful life events are associated with increased bone loss. Four thousand three hundred eighty-eight men aged ≥65 years in the Osteoporotic Fractures in Men study completed total hip bone mineral density (BMD) measures at baseline and visit 2, approximately 4.6 years later, and self-reported stressful life events data mid-way between baseline and visit 2, and at visit 2. We used linear regression to model the association of stressful life events with concurrent annualized total hip BMD loss, and log binomial regression or Poisson regression to model risk of concurrent accelerated BMD loss (>1 SD more than mean annualized change). Men (75.3 %) reported ≥1 type of stressful life event, including 43.3 % with ≥2 types of stressful life events. Mean annualized BMD loss was -0.36 % (SD 0.88), and 13.9 % of men were categorized with accelerated BMD loss (about 5.7 % or more total loss). Rate of annualized BMD loss increased with the number of types of stressful life events after adjustment for age (p < 0.001), but not after multivariable adjustment (p = 0.07). Multivariable-adjusted risk of accelerated BMD loss increased with the number of types of stressful life events (RR, 1.10 [95 % confidence interval (CI), 1.04-1.16]) per increase of one type of stressful life event). Fracture risk was not significantly different between stressful life event-accelerated bone loss subgroups (p = 0.08). In these older men, stressful life events were associated with a small, dose-related increase in risk of concurrent accelerated hip bone loss. Low frequency of fractures limited assessment of whether rapid bone loss mediates any association of stressful life events with incident fractures. Future studies are needed to confirm these findings and to investigate the mechanism that may underlie this association.

Moderate zinc supplementation during prolonged steroid therapy exacerbates bone loss in rats.

The present study was conducted to understand the influence of zinc on bone mineral metabolism in prednisolone-treated rats. Disturbance in bone mineral metabolism was induced in rats by subjecting them to prednisolone treatment for a period of 8 weeks. Female rats aged 6-8 weeks weighing 150 to 200 g were divided into four treatment groups, viz., normal control, prednisolone-treated (40 mg/kg body weight orally, thrice a week), zinc-treated (227 mg/L in drinking water, daily), and combined prednisolone + zinc-treated groups. Parameters such as changes in mineral levels in the bone and serum, bone mineral density (BMD), bone mineral content (BMC), and bone 99m-technetium-labeled methylene diphosphonate ((99m)Tc-MDP) uptake were studied in various treatment groups. Prednisolone treatment caused an appreciable decrease in calcium levels both in the bone and serum and also in bone dry weight, BMC, and BMD in rats. Prednisolone-treated rats when supplemented with zinc showed further reduction in calcium levels, bone dry weight, BMD, and BMC. The study therefore revealed that moderate intake of zinc as a nutritional supplement during steroid therapy could enhance calcium deficiency in the body and accelerate bone loss.

Depression, antidepressants, and bone health in older adults: a systematic review.

To examine the association between depression, antidepressant use, and bone health in older adults and the implications for treatment. Systematic review. All studies that measured depression or antidepressant exposure and bone mineral density (BMD). Adults aged 60 and older. Age, site of BMD measurement using dual-energy X-ray absorptiometry (DXA), measure of depression or depressive symptoms, association between BMD changes, and depression or antidepressant use. Nineteen observational studies met the final inclusion criteria; no experimental studies were found. Several cross-sectional and longitudinal studies found that depression or depressive symptoms were associated with a decrease in BMD. Few studies and only two longitudinal studies addressed the association between serotonin reuptake inhibitor (SRI) antidepressant use and a decrease in BMD and they had conflicting results. Depression and depressive symptoms are associated with low bone mass and accelerated bone loss in older adults; putative mechanisms underlying this relationship are discussed. There is insufficient evidence that SRI antidepressants adversely affect bone health. Thus, a change in current recommendations for the use of antidepressants in older adults is not justified at the present time. Given the high public health significance of this question, more studies are required to determine whether (and in whom) antidepressants may be deleterious for bone health.

Effects of escitalopram on markers of bone turnover: a randomized clinical trial.

Recent observational studies have suggested that the use of selective serotonin reuptake inhibitors is associated with an increased fracture risk and an accelerated bone loss, although conflicting results have been reported. Furthermore, because many of these studies have been performed in depressed women, confounding by indication may influence these findings. The objective of the study was to determine whether selective serotonin reuptake inhibitors affect bone metabolism Design: This was a randomized controlled trial. The study was conducted in four US clinical sites. Healthy peri- and postmenopausal women participated in the study. The intervention was escitalopram (10-20 mg/d) for the treatment of vasomotor symptoms. Serum carboxyterminal collagen crosslinks (CTX) and serum amino-terminal propeptide of type I collagen (P1NP) were measured. One hundred forty-one peri- or postmenopausal nondepressed women (mean age 53.7 y, SD 4.1) had baseline and 8-week follow-up samples available for analysis and were included in the study (69 escitalopram, 72 placebo). The groups were balanced across a broad range of baseline characteristics, including age, race, body mass index, smoking status, and mood symptoms. The between-group differences in the change in CTX and P1NP from baseline to week 8 were compared by a repeated-measures linear regression model adjusted for race, clinical center, and baseline measurement. Treatment with escitalopram reduced serum P1NP by 1.02 ng/mL on average [95% confidence interval (CI) -5.17, 3.12] compared with a reduction of 1.88 ng/mL (95% CI -4.82, 1.06) in the placebo group (P = .65). Similarly, serum CTX decreased 0.02 ng/mL on average (95% CI -0.05, 0.01) in the escitalopram group compared with 0.00 ng/mL (95% CI -0.02, 0.02) in the placebo group (P = .24). The results were similar when the analysis was restricted to those women whose adherence to study medication was 70% or greater. Although the study was limited to 8 weeks, these results suggest that escitalopram does not significantly alter bone metabolism in the short term.

A survey of steroid-related osteoporosis diagnosis, prevention and treatment practices of pediatric rheumatologists in North America.

BackgroundThe purpose of our study is to assess practices of North American pediatric rheumatologists regarding monitoring, prevention, and treatment of low bone mineral density (BMD) in children on long-term glucocorticoid treatment.Long-term glucocorticoid therapy is associated with accelerated bone loss. Children with JIA and lupus have low baseline BMD and incident vertebral fractures commonly occur in these groups of patients even after a relatively short period of time being on systemic glucocorticoids. There are no established guidelines for identification, prevention, and treatment of glucocorticoid-induced bone loss in children.MethodsA cross-sectional online survey was conducted with 199 physicians who were listed in the ACR database as practicing pediatric rheumatology in North America.Results86 physicians (43%) responded; 87% were board-certified in pediatric rheumatology. 95% used dual energy X-ray absorptiometry as their primary modality for assessing BMD. 79% “rarely” or “never” obtained a baseline BMD measurement prior to initiation of glucocorticoid therapy. 42% of respondents followed BMD annually. 93% “frequently” or “always” prescribed calcium for patients on long-term corticosteroid therapy; 81% “frequently” or “always” prescribed vitamin D. In patients diagnosed with osteoporosis, 35%-50 % of the practitioners “sometimes”, “frequently” or “always” prescribed bisphosphonates. Bisphosphonates are prescribed at similar rates for male and female patients, and slightly more frequently for pubertal than for pre-pubertal patients. 96% of respondents “rarely” or “never” prescribed calcitonin for patients on long-term glucocorticoid therapy; 92% “rarely” or “never” prescribe this medication for patients with known osteopenia or osteoporosis.ConclusionsUtilization of DXA in children on long-term corticosteroid therapy varies greatly among North American pediatric rheumatologists. Most respondents do not screen for low BMD on a regular basis despite acknowledging the risks of bone loss in this population. Broad consensus appears to be present among practitioners favoring the prescription of calcium and vitamin D for patients receiving long-term corticosteroid therapy. Relatively few respondents consistently recommend bisphosphonate therapy, even for patients with known low bone density; calcitonin is rarely used. These data underscore the need for studies to acquire specific data on bone loss, and its prevention and treatment in young patients on long-term glucocorticoid therapy.

SP0132 How to Assess Glucocorticoid Confounding in the Context of Osteoporosis

Opinions on the value of glucocorticoids (GCs) have fluctuated between euphoric acceptance and outright rejection. This ambivalence of opinion arose because of their important clinical effects on one hand, and...

The assessment of bone mineral content and density of the lumbar spine and proximal femur in US submariners.

The submarine environment is unique in that there is limited space and no sunlight, which may negatively affect skeletal health and lead to accelerated bone loss, osteoporosis, and fractures. The primary purpose of this study was to determine whether there was an association with submarine service, specifically time spent at sea, and bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine and dual proximal femur (total hip and femoral neck) measured by DXA. This is a cross-sectional study of 462 submariners 20-91years old. Variables included in the analysis were age, height, race, alcohol intake, tobacco use, fracture history, conditions, and medications known to cause bone loss and osteoporosis and submarine service. Of the submarine service predictors, only serving onboard a diesel submarine was determined to be independently associated with a reduction in BMD of the total hip and femur neck, while no submarine service predictor increased the odds of having low BMD. In submariners 50+ years old, the age-adjusted prevalence of osteopenia was 15.7% (lumbar spine) and 40.4% (femur neck), while the prevalence of osteoporosis was 4.8% (lumbar spine) and 4.2% (femur neck), rates that did not differ from NHANES 2005-2008. In submariners <50years old, 3.1% was below the expected range for age. The proportion of submariners 50+ years old that met the FRAX criteria for pharmacological treatment was 12%. Intermittent periods of submergence that can range from a few days to 3+ months do not appear to compromise skeletal health differently than the general population.