Gain In Bone Mineral Density Research Articles

Bone mineral density and growth in children with coeliac disease on a gluten free-diet.

To evaluate changes in growth and bone metabolism during consumption of a gluten-free diet (GFD) in children with coeliac disease (CD). Thirty-seven children with CD (mean age of 8.8 ± 4.6 years, 21 girls) were enrolled. Anthropometric measurements, bone mineral density (BMD) in lumbar 2-4 vertebrae, and serum alkaline phosphatase, calcium, and phosphorus levels at diagnosis and at follow-up were recorded. The mean follow-up period was 3.5 ± 2.3 years. The BMD of patients was significantly lower than that of control subjects at the time of diagnosis but not after 1 year of the GFD. Incidence of low BMD with respect to z-scores for chronological age (CA) was significantly higher than z-scores for height age (HA) (P = 0.006). At the first year of GFD, BMD, BMD z-score, height-for-age z-scores, and weight-for-age z-scores were significantly increased compared with the baseline, but not after 1 year of the GFD. In CD, the first year of GFD is important in weight gain, linear growth, and improvement of BMD. A considerable relation of low BMD in children with CD, with respect to z-scores for CA, may be a result of misinterpretation of low BMD due to short stature.

Twelve-Minute Daily Yoga Regimen Reverses Osteoporotic Bone Loss.

Objective:Assess the effectiveness of selected yoga postures in raising bone mineral density (BMD).Methods:Ten-year study of 741 Internet-recruited volunteers comparing preyoga BMD changes with postyoga BMD changes.Outcome Measures:Dual-energy x-ray absorptiometric scans. Optional radiographs of hips and spine and bone quality study (7 Tesla).Results:Bone mineral density improved in spine, hips, and femur of the 227 moderately and fully compliant patients. Monthly gain in BMD was significant in spine (0.0029 g/cm2, P = .005) and femur (0.00022 g/cm2, P = .053), but in 1 cohort, although mean gain in hip BMD was 50%, large individual differences raised the confidence interval and the gain was not significant for total hip (0.000357 g/cm2). No yoga-related serious injuries were imaged or reported. Bone quality appeared qualitatively improved in yoga practitioners.Conclusion:Yoga appears to raise BMD in the spine and the femur safely.

BONE DENSITY PARAMETERS CHANGING IN POSTMENOPAUSAL WOMEN WITH DIFFUSE SITES NONTOXIC GOITER AND AUTOIMMUNE THYROIDITIS IN TREATMENTLOW-DOSE ESTROGEN-PROGESTOGENS MEDICATION

Postmenopausal osteoporosis - multifactorial disease, on the pathogenesis of which affect not only the estrogen deficiency, but functional state of other endocrine glands, particularly the thyroid gland. The article presents the results of a research 74 women with autoimmune thyroiditis and diffuse nodular nontoxic goiter, which during perimenopause and menopause for 12 months received low-dose estrogen-progestin preparation containing 2 mg drospirenone and 1 mg of 17-estradiol. The control group consisted of 40 women of similar age without thyroid disease who were not receiving drugs hormone replacement therapy (HRT). To study the effect of HRT on bone metabolism all women at baseline and after 12 months of follow-conducted study of bone mineral density (BMD) with dual en ergy X-ray absorptiometry (DXA). As a result of the treatment received reliable increase in BMD in the lumbar spine L1-L4 9-10% (p <0.001) in the proximal femur - by 2.8-3.5% (p <0.01) in the bones forearm - by 1.8-2.1% (p <0.01).Conclusion: The use of low-dose estrogen-progestin drugs for 12 months in women with autoimmune thyroiditis and diffuse nodular nontoxic goiter in peri- and postmenopausal period helped gain in BMD in both trabecular and cortical bone structure.

Evaluation of using microplates osteosynthesis for pediatric mandibular fractures

ObjectiveThe purpose of this study was to evaluate both clinically and radiographically using of two microplates in treatment of displaced pediatric mandibular fractures. Materials & methodsThis study included ten children had displaced mandibular fracture with age ranged between (4–11) years were treated using two microplates and microscrews through intraoral approach. All children were examined preoperative clinically and radiographically by panoramic view and computed tomography (CT) or lower occlusal view. All children were evaluated postoperative clinically at one week, one and three months for wound healing, occlusion, infection, nerve affection and stability of fracture and radiographically by panoramic view at second postoperative day, one and three months and by quantitative CT at one and three months to evaluate the accuracy of reduction and bone healing at fracture line. ResultsClinically there were no complications in all cases overall follow up period except for two cases showing occlusal discrepancy treated with guiding elastics. Radiographic results showed that good alignment of fracture segments horizontally and vertically without displacement and significant increase in bone mineral density gain after one and three months. ConclusionTitanium microplates provide adequate stability for fracture segments in treatment of pediatric mandibular fracture. Low profile and malleability of microplates allow adaptation to mandible easily and minimize the possibility of trauma to teeth buds.

Vitamin D and bone mineral density changes in postmenopausal women treated with strontium ranelate.

Vitamin D deficiency is widespread and often reported in subjects treated for osteoporosis. Optimal vitamin D repletion was previously shown to maximize the efficacy of anti-resorptive agents. To date, no information exists about the role of vitamin D in the response to strontium ranelate (SrR) treatment. The aim of our study was to investigate the BMD response to SrR in accordance with change of vitamin D status. A retrospective analysis of 108 women receiving SrR for postmenopausal osteoporosis was carried out. Women were treated with SrR (2 g/day), with cholecalciferol (25,000 IU biweekly) and calcium carbonate as appropriate. Lumbar spine and femoral neck BMD, bone formation markers (BGP, ALP), resorption marker (OH-PRO) and serum 25(OH)D were measured at baseline after 18-months. All participants were divided into two groups according to the median variation of 25(OH)D over the observation period. SrR was associated with improvement of BMD at lumbar spine (p < 0.0001) and to a non significant variation at femoral neck (p = 0.2). Only subjects with Δ25(OH)D > 6.14 %, reported a significant BMD gain at femoral neck (p = 0.03). Change of BMD at femoral neck was positively associated with modification of ALP (r = 0.28, p = 0.01). This association was not maintained when considering only women with Δ25(OH)D < 6.14 % (r = 0.28, p = 0.09). At a multiple regression analysis, ALP change was the only predictor of femoral neck BMD modification (β 0.13; SE 0.05; p = 0.01). Improvement of vitamin D status was associated with enhancement of BMD response to SrR in women with postmenopausal osteoporosis, in particular, at femoral neck.

Switching of oral bisphosphonates to denosumab in chronic glucocorticoid users: A 12-month randomized controlled trial

ObjectivesTo evaluate the effect of switching from oral bisphosphonates to denosumab on bone mineral density (BMD) in long-term glucocorticoid users. MethodsAdult patients who were receiving long-term prednisolone (≥2.5mg/day for ≥1year) and oral bisphosphonates (≥2years) were recruited. Participants were randomized to either continue oral bisphosphonates or switch to denosumab (60mg subcutaneously every 6months) for 12months. Serial BMD (lumbar spine, hip) and bone turnover markers (serum osteocalcin, P1NP, β-CTX) were measured. Results42 women were recruited (age 54.7±12.9years; 21 shifted to denosumab and 21 continued on bisphosphonates). The duration of prednisolone therapy was 101±66.3months and the daily dose was 4.4±2.1mg. Baseline demographic data, osteoporosis risk factors, and BMD at various sites were similar between the two groups of patients. At month 12, BMD of the spine and hip increased by +3.4±0.9% (p=0.002) and +1.4±0.6% (p=0.03), respectively, in the denosumab group; whereas the corresponding change was +1.5±0.4% (p=0.001) and +0.80±0.5% (p=0.12) in the bisphosphonate group. The spinal BMD at month 12 was significantly higher in the denosumab than bisphosphonate group after adjustment for baseline BMD and β-CTX values, and other confounding factors (p=0.01). Bone turnover markers (β-CTX and P1NP) were more strongly suppressed by denosumab than the bisphosphonates. Minor infections were more common in denosumab-treated patients while other adverse events occurred at similar frequencies between the two groups. ConclusionsIn patients receiving long-term glucocorticoids, switching from oral bisphosphonates to denosumab resulted in greater gain of the spinal BMD and suppression of bone turnover markers after 12months of therapy. The results have to be confirmed by a larger clinical trial with fracture as endpoint.

On the mark? Is alkaline phosphatase a surrogate for bone density in men with hypogonadism?

The current issue of the BJUI contains a paper by Dubaja et al. 1 that may be of interest to physicians who have patients with hypogonadism. The authors speak to an unappreciated aspect of low testosterone; namely, the loss of bone in men and the possible recovery with treatment. Their retrospective study looked at 140 men with hypogonadism treated with exogenous testosterone replacement or clomiphene citrate testosterone enhancement. These men were also assessed for bone mineral density (BMD) markers at 6, 12 and 24 months after initial treatment. Importantly, dual-energy X-ray absorptiometry (DEXA) was performed a second time after 2 treatment years for a subset of these men. DEXA showed that there was a gain in BMD and a loss of serum alkaline phosphatase (AP) for all the men over time. The loss of AP was rapid but stabilized at 6 months. Testosterone and free testosterone increased as expected but there were no changes in vitamin D, calcium, parathyroid hormone or sex hormone-binding globulin. There was a correlation between AP and testosterone. The authors recognized poor bone density at baseline in those men with testosterone levels <250 ng/dl. Bone mineral density is the best way to predict osteoporosis and fragility fractures 2. Women loose BMD after menopause and that is accompanied by many changes, including gains in AP 3. The decline in serum oestrogens is a factor for women, and oestrogen replacement therapy historically has been used to prevent that loss. Not all men undergo a similar loss, i.e. andropause is not recognized in the same way as menopause. Even though osteoporosis is less common in men, the associated comorbidity may be more significant. There is an age-related decline in testosterone and an acute loss for some men such that they approach their physicians with symptoms. The underlying cause of bone loss in men and women may be the same: serum oestrogen loss. Men who lose testosterone are also losing oestrogen because testosterone is the precursor via aromatase. Repros Therapeutics is developing a way to treat men with secondary hypogonadism. An ongoing 1-year DEXA study recruited eligible men. Key inclusion factors were age < 60 years and body mass index > 25 kg/m2. Remarkably 24% of men failed the screening test because of osteopenia, despite the fact that few of them were old or underweight. The present paper by Dubaja et al. suggests that a readily available serum test may be able to monitor men on testosterone therapies for gain in BMD. Given the relatively low incidence of osteoporosis, screening every man by DEXA is not cost-efficient. The 1 year or more needed to find BMD loss by DEXA also wastes time and resources. Quantitative CT is more costly and is accompanied by high radiation exposure. The use of AP, as suggested in the present study, may represent a reasonable alternative. The paper is not without its weaknesses. There was no indication of whether these men had primary or secondary hypogonadism. Transdermal testosterone should raise testosterone and oestrogen in both groups of men whereas clomiphene citrate works through changes in LH and FSH and requires an intact hypothalamic-pituitary-gonadal axis (useful in men with secondary hypogonadism only). Indeed, the two kinds of treatment will have the opposite effect on LH and FSH 4. The authors recognized the importance of Leydig cells in producing testosterone, yet the effects of a transdermal testosterone would be to shut down testosterone production. We commend their suggestion that other factors that contribute to both bone and Leydig cell function, insulin-like 3 5 and osteocalcin 6 should be studied in relation to AP. The loss of subjects throughout the 2 years was troubling, but it is known that men on transdermal treatments discontinue with disturbing frequency despite satisfaction 7. If those who stayed in the present study were those with the best outcomes in terms of testosterone and BMD, potential bias may exist. If men can be encouraged to continue therapy through positive effects on BMD being detected as early as 6 months, AP monitoring may improve patient compliance. Only DEXA can give that assurance now. The authors noted the need for a larger prospective trial. Nevertheless, their paper provides a rationale for monitoring men on testosterone therapies that can be implemented with minimal cost or the need for new diagnostics. Authors are employees and/or stockholders in Repros Therapeutics.

Sustained Modeling-Based Bone Formation During Adulthood in Cynomolgus Monkeys May Contribute to Continuous BMD Gains With Denosumab.

Denosumab (DMAb) administration to postmenopausal women with osteoporosis is associated with continued bone mineral density (BMD) increases and low fracture incidence through 8 years, despite persistently reduced bone turnover markers and limited fluorochrome labeling in iliac crest bone biopsies. BMD increases were hypothesized to result from additional accrual of bone matrix via modeling-based bone formation-a hypothesis that was tested by examining fluorochrome labeling patterns in sections from ovariectomized (OVX) cynomolgus monkeys (cynos) treated with DMAb for 16 months. Mature OVX or Sham cynos were treated monthly with vehicle for 16 months, whereas other OVX cynos received monthly 25 or 50 mg/kg DMAb. DMAb groups exhibited very low serum bone resorption and formation biomarkers and near-absent fluorochrome labeling in proximal femur cancellous bone. Despite these reductions, femoral neck dual-energy X-ray absorptiometry (DXA) BMD continued to rise in DMAb-treated cynos, from a 4.6% increase at month 6 to 9.8% above baseline at month 16. Further examination of cortical bone in the proximal femur demonstrated consistent and prominent labeling on the superior endocortex and the inferior periosteal surface, typically containing multiple superimposed labels from month 6 to 16 over smooth cement lines, consistent with continuous modeling-based bone formation. These findings were evident in all groups. Quantitative analysis at another modeling site, the ninth rib, demonstrated that DMAb did not alter the surface extent of modeling-based labels, or the cortical area bound by them, relative to OVX controls, while significantly reducing remodeling-based bone formation and eroded surface. This conservation of modeling-based formation occurred concomitantly with increased femoral neck strength and, when coupled with a reduction in remodeling-based bone loss, is likely to contribute to increases in bone mass with DMAb treatment. Thus, this study provides preclinical evidence for a potential mechanism that could contribute to the clinical observations of continued BMD increases and low fracture rates with long-term DMAb administration.

Change of Bone Mineral Density and Biochemical Markers of Bone Turnover in Patients on Suppressive Levothyroxine Therapy for Differentiated Thyroid Carcinoma.

Untreated hyperthyroidism and high-dose thyroid hormone are associated with osteoporosis, and increased bone mineral density (BMD) has been demonstrated in postmenopausal females with hypoparathyroidism. Studies on the effect of suppressive levothyroxine (LT4) therapy on BMD and bone metabolism after total thyroidectomy in patients with differentiated thyroid carcinoma have presented conflicting results, and few studies in relation to the status of hypoparathyroidism have been studied. One hundred postmenopausal women and 24 premenopausal women on LT4 suppression therapy were included in this study. BMD of lumbar spine and femur and bone turnover markers were measured at the baseline and during the follow-up period up to 18 months using dual energy X-ray absorptiometry. Biochemical marker of bone resorption was measured by urine deoxypyridinoline and bone formation by serum osteocalcin. The age ranged from 36 to 64 years old. Thyroid stimulating hormone (TSH) was suppressed during the study. The results showed that BMD of femur and lumbar spine were not significantly changed in both pre- and postmenopausal women except femur neck in postmenopausal women without hypoparathyroidism. Patients with hypoparathyroidism had higher BMD gain than those without hypoparathyroidism in total hip (1.25 vs. -1.18%, P=0.015). Biochemical markers of bone turnover, serum osteocalcin, and urine deoxypyridinoline did not show significant change. In conclusion, patients with well differentiated thyroid carcinoma are not at a great risk of bone loss after LT4 suppressive therapy. The state of hypoparathyroidism is associated with increased BMD, particularly in postmenopausal women.

Effect of Alendronate on Bone Mineral Density in Post Menopausal Women with Type 2 Diabetes Mellitus

Aim: To perform a retrospective study to determine the effect of Bisphophanates on bone mineral density (BMD) in the late post-menopausal (PM) osteoporatic and osteopenic women with Type 2 Diabetes Mellitus (DM). Method: In this retrospective case control study, 114 PM diabetic women over age 65 who took alendronate for at least 3 years, 43 of them had osteoporosis and 71 with osteopenia. The efficacy of therapy was measured by comparing a minimum of two BMD studies. Result: The study (n=114) demonstrated statistically significant BMD gain (+3.1% and +1.9%) at the spine and hip respectively but statistically significant loss of BMD (-9.8%) at forearm (FA). There was statistically significant correlation between body mass index (BMI) and BMD, in spine and hip but not in FA. We found negative correlation between A1C and BMD at all 3 sites, with a statically significant correlation observed at FA. Conclusion: It appears that Bisphosphonates are not effective in preventing bone loss in the FA of diabetic post-menopausal women. In addition bisphosphonates therapy resulted in significant gains of BMD at the spine and hip. A larger study should be done to compare bisphosphonates to other modalities of therapy for osteoporosis in diabetic post menopausal patients.

Increased Bone Mineral Density with Monthly Intravenous Ibandronate Contributes to Fracture Risk Reduction in Patients with Primary Osteoporosis: Three-Year Analysis of the MOVER Study

The relationship between gains in bone mineral density (BMD) in the hip and the incidence of vertebral fractures in the MOVER study was examined. Japanese patients from the ibandronate and risedronate treatment groups whose hip BMD had increased during the 3-year treatment period were classified into those with or without vertebral fractures. In both the ibandronate group and the risedronate group, hip BMD gains in the patients who had developed no vertebral fractures during the treatment period were greater than in the patients who developed vertebral fractures. We categorized the gains in hip BMD at 6 months into 3 groups (≤0, >0 to ≤3, and >3 %), and used logistic regression analysis to estimate odds ratios and the probabilities of incidence of vertebral fractures at 12, 24, and 36 months. The current study demonstrated that greater gains in hip BMD during the first 6 months of treatment were associated with a reduction in the risk of subsequent vertebral fractures during the duration of treatment, and suggested that measurement of hip BMD gain at that time could lead to a prediction of the risk of the future vertebral fracture incidence.

High fat diet promotes achievement of peak bone mass in young rats

The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fat mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet.

Lower P1NP serum levels: a predictive marker of bone loss after 1year follow-up in premenopausal systemic lupus erythematosus patients.

Predictors of bone mineral density (BMD) loss are additional tools in the management of osteoporosis in premenopausal women with systemic lupus erythematosus (SLE). This study provides original evidence that N-terminal propeptide of type 1 collagen (P1NP), the most specific bone formation marker, is a predictor of BMD loss in this group of women. SLE is associated with a high risk of low bone mass/fractures but this risk is still controversial in premenopausal women. Our aim was to determine the 1 year incidence of BMD loss in premenopausal SLE women and the value of bone turnover markers as predictors of this complication. This study enrolled a convenience sample of 63 premenopausal SLE patients. BMD was evaluated by dual X-ray absorptiometry at lumbar spine and hip at baseline and after 12 months. BMD changes above the least significant change were considered significant. Serum levels of P1NP and CTX (electrochemiluminescence), OPG, and RANKL (ELISA) were determined at baseline. Mean age was 31.1±6.8 years, and disease duration was 5.25±3.8 years. 36.5 % of patients presented BMD loss and 17.5 % BMD gain at lumbar spine and/or hip. Patients were divided in three groups: BMD loss (BL), no BMD change (NC), and BMD gain (BG). Patients with BL and NC received similar cumulative/mean/maximum glucocorticoid doses during the study, but patients with BG received lower doses (p<0.05). Baseline P1NP levels were different in the groups (BL: 36.95±23.37 vs. NC: 54.63±30.82 vs. BG: 84.09±43.85 ng/mL; p=0.031 BL vs. NC, p<0.001 BL vs. BG, and p=0.039 NC vs. BG). There was no difference in CTX, OPG, or RANKL levels. After multivariate analysis, P1NP remained as an independent risk factor for BMD loss (p<0.03). This study provides original evidence that lower levels of P1NP, the most specific bone formation marker, are predictive of BMD loss over 12 months in premenopausal SLE patients.

Research in brief

Findings of a multifaceted study have provided new insight into the role of lipolytic pathways in metabolic health. Using gene sequencing in 24 people in an Amish population who had extremely high or low fasting triglycerides, investigators identified a frameshift deletion in exon 9 of the gene encoding hormone-sensitive lipase (LIPE) in one individual with high trigyceride concentrations. In a cohort of 2738 Amish individuals, 140 were heterozygous for the deletion and one was homozygous. Compared with non-carriers, carriers of the frameshift deletion had higher insulin resistance (p=0·005), serum triglyceride concentrations (p=0·003), and hepatic fat content (p<0·001), and lower HDL cholesterol concentrations (p<0·001). The prevalence of type 2 diabetes in heterozygous carriers was 11·4% compared with 6·8% in individuals who were not carriers (p=0·02). According to investigators, bariatric surgery might be associated with long-term remission of diabetes. Using data from the Swedish Obese Study, the researchers compared long-term those for 343 patients with type 2 diabetes who underwent surgery with outcomes for a control group of 260 obese patients with type 2 diabetes. At 2 years, a greater proportion of people in the surgery group were in diabetes remission than in the control group (72.3% vs 16.4%; unadjusted odds ratio 13·3, 95% CI 8·5–20·7). At 15 years follow-up, the proportion of patients in the surgery group who were in remission decreased (30·4%), but these patients were still more likely to be in remission than were those in the control group (odds ratio 6·3, 95% CI 2·1–18·9). Over a 20 year follow-up period, the surgery group was also less likely to develop macrovascular and microvascular complications. A study by Maahs and colleagues has shown differences in the management of children with type 1 diabetes from either the USA or Germany and Austria. Using data from the US T1DX registry (674 patients) and German–Austrian DPV registry (1948 patients), characteristics and clinical outcomes for children younger than 6 years with type 1 diabetes were compared. Mean HbA1c concentrations in children in T1DX were higher than those in individuals in DPV (8·2% vs 7·4%, p<0·001); notably a larger proportion of patients in DPV were receiving insulin pump therapy compared with patients from T1DX (74% vs 50%, p<0·001). The authors of a US retrospective cohort study have attempted to address whether people with type 2 diabetes who are failing on metformin monotherapy should receive insulin or a sulfonylurea as second-line therapy. Investigators ascertained rates of cardiovascular events and death in veterans started on metformin between 2001 and 2008 and who later received a sulfonylurea or insulin. Participants were observed until 2011. The analysis included 2436 patients receiving metformin plus insulin and 12 180 receiving metformin plus a sulfonylurea. There was increased risk of a composite of cardiovascular outcomes and all-cause mortality for individuals in the insulin group compared with individuals in the sulfonylurea group (42·7 vs 32·8 events per 1000 person-years; adjusted hazard ratio 1·30, 95% CI 1·07–1·58). The risk of death from any cause was lower for individuals in the sulfonylurea group than for those in the insulin group (22·7 vs 33·7 per 1000 person-years; adjusted hazard ratio 1·44, 95% CI 1·15–1·79). When added to metformin, GLP-1 receptor agonist albiglutide might result in greater improvements in HbA1c concentration than addition of DPP-4 inhibitor sitagliptin or sulfonylurea glimepiride. In the 104 week, double-blind, placebo and active controlled HARMONY 3 trial, patients with type 2 diabetes taking metformin were randomised to receive weekly albiglutide (n=302), daily sitagliptin (n=302), daily glimepiride (n=307), or placebo (n=101). Participants receiving albiglutide had greater reductions in HbA1c at 104 weeks than did those receiving sitagliptin (mean difference −0·4%; p=0·0001), glimepiride (–0·3%; p=0·0033), or placebo (–0·9%; p<0·0001). The rate of adverse events and serious adverse events was generally similar between the four groups. Results from a randomised clinical trial have provided some hope for young women with primary ovarian insufficiency. In the study of women with primary ovarian insufficiency aged between 18 and 42 years, investigators assessed the effect of treatment with transdermal estradiol, cyclical oral progesterone, and placebo (n=72) versus treatment with estradiol, progesterone, and transdermal testosterone (n=73) on bone mineral density. They also included a control group (n=70) of women with normal ovarian function. Although the trial was terminated early because of futility of testosterone on the primary outcome, women receiving estradiol, progesterone, and placebo had about a 2·45% gain in bone mineral density at the femoral neck compared with a 2·61% loss in control individuals (p=0·0002) during the 3 year follow-up.

OP0260 Denosumab for Patients Receiving Long-Term Glucocorticoids Who do not Have Adequate Response to Bisphosphonate Treatment: A Randomized Controlled Trial

ObjectivesTo evaluate the efficacy of denosumab on bone mineral density (BMD) in patients receiving long-term glucocorticoids who do not have satisfactory response to bisphosphonate treatment.MethodsPatients who were receiving long-term prednisolone...

SAT0492 Risedronate for Prevention of Steroid Induced Osteoporosis in Rheumatoid Arthritis Pacients

BackgroundCorticosteroids are widely used to suppress hyperactive inflammation in rheumatoid arthritis (RA). Bone loss is a serious side effect of this therapy. Risedronate is frequently used fo prevention and treatment...

SAT0480 Effects of A Previous Treatment With18 Months of Teriparatide on the Cortical Bone Mineral Density Response to Three Years of Bisphosphonate Treatment in Severe Osteoporosis

BackgroundThe actual challenge in the management of the severe osteoporosis is to find the best therapeutic strategy to increase bone mineral density (BMD) at the cortical sites, where gains with...

Bone mineral density changes following discontinuation of ronacaleret treatment: Off-treatment extension of a randomized, dose-finding phase II trial

ContextParathyroidectomy in patients with hyperparathyroidism can produce subsequent increases in bone mineral density (BMD). Ronacaleret, a selective calcium-sensing receptor antagonist that stimulates endogenous parathyroid hormone release, induced mild hyperparathyroidism. ObjectiveThe aim of this study is to evaluate whether BMD changes after cessation of ronacaleret treatment. DesignObservational, off-treatment, extension of a randomized, placebo-controlled, dose-ranging phase II trial. SettingFifteen academic centers in seven countries. PatientsPostmenopausal women with low BMD; 171 out of 569 women in the parent study were enrolled in the extension study. InterventionsSubjects were treated with ronacaleret 100mg (n=16), 200mg (n=38), 300mg (n=35), or 400mg (n=32) once daily, alendronate 70mg (n=17) once weekly, or matching placebo (n=33) for 10–12months; BMD was measured after discontinuation of ronacaleret or alendronate treatment. Main outcome measureMean percent change in lumbar spine areal BMD by dual-energy X-ray absorptiometry at 6–12months after discontinuing ronacaleret or alendronate compared with the 10- to 12-month BMD measurement of the parent study. ResultsAt the lumbar spine, all doses of ronacaleret resulted in gains in BMD while on treatment. These increases in BMD were maintained or increased after discontinuation of ronacaleret. All doses of ronacaleret caused bone loss at the total hip while on active treatment. However, there was an attenuation of this loss in the off-treatment extension study. ConclusionThe gain in BMD at the lumbar spine was maintained post-treatment and the loss of BMD at the total hip was attenuated. We hypothesize that there may have been some bone remineralization after cessation of ronacaleret.

Individual site-specific bone mineral density gain in normocalcemic primary hyperparathyroidism

In this study, we show that successful parathyroidectomy is followed at 1year by a significant individual bone mineral density (BMD) gain in nearly half of normocalcemic PHPT patients with reduced bone mass. Alkaline phosphatase levels above median were identified as an independent predictor of individual BMD gain in normocalcemic PHPT patients. The aims of this study were to assess bone mineral density (BMD) gains after parathyroidectomy (PTX) in normocalcemic primary hyperparathyroidism (PHPT) at the individual level and to identify predictors of BMD gain after PTX in this context. Longitudinal cohort study of 55 PHPT patients referred for low bone mass and mild abnormalities of calcium/phosphorus metabolism, and successfully treated by PTX. BMD gain at 1year was considered significant if ≥0.030g/cm(2) at one site or more, without any equivalent BMD loss at another site. A logistic regression analysis was performed to identify predictive factors of individual BMD gain. Among the 55 PHPT patients included, 29 patients with hypercalcemia, 36 patients with normocalcemic PHPT, defined by normal pre-PTX serum total (albumin-corrected) calcium (tCa), including 15 patients with normal ionized calcium (iCa), were identified. At 1year of PTX, an individual BMD gain was observed in 73.7% of hypercalcemic, 44.4% of normocalcemic, and 46% of PHPTpatients with both normal tCa and iCa. Site-specific BMD gains were most important at the spine and hip in all subgroups including patients with normal iCa. Alkaline phosphatase activity above median, which reflects high bone turnover, was predictive of individual BMD gain, both in the overall cohort (OR = 4.9, 95% CI 1.3-18.9), and in the normocalcemic group: OR = 8.4, 95% CI 1.4-56.6. Successful PTX is followed at 1year by a significant individual BMD gain in nearly half of normocalcemic PHPT patients with osteoporosis. ALP levels above median could contribute to the therapeutic decision in this context.

Effect of raloxifene on disease activity and vascular biomarkers in patients with systemic lupus erythematosus: Subgroup analysis of a double-blind randomized controlled trial

The purpose of this study was to identify the effect of raloxifene on disease activity and vascular biomarkers in patients with systemic lupus erythematosus (SLE). Subgroup data were analyzed for postmenopausal female SLE patients who participated in a randomized controlled trial of raloxifene on glucocorticoid-induced osteoporosis. Patients who were receiving a stable daily dose of prednisolone (≤10 mg) for ≥6 months were assigned to receive raloxifene (60 mg/day) or placebo on top of calcium and vitamin D. Disease activity was assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA), SLE disease activity index (SLEDAI) and physicians' global assessment (PGA) every three months. Lupus flares were assessed by the SELENA flare instrument. Serial serum levels of homocysteine, high-sensitivity C-reactive protein (hsCRP) and soluble thrombomodulin (sTM) were measured. A total of 62 patients (30 raloxifene, 32 placebo) were studied (age 52.5 ± 6.7 years; SLE duration 9.3 ± 7.6 years; menopause duration 7.2 ± 6.6 years). The SLEDAI at entry was 1.8 ± 2.3 (SLEDAI ≥ 6 in 8%). After 12 months, a significant gain in bone mineral density (BMD) of the lumbar spine (1.6%, p = 0.02), and reduction in bone resorption and formation markers was observed in the raloxifene but not in the placebo treated patients. The SELENA-SLEDAI and PGA scores area under the curve over 12 months were not significantly different between the two groups. There were three episodes of mild/moderate lupus flares (33% musculoskeletal, 33% dermatological) in the raloxifene group, compared to nine episodes of mild/moderate flares (27% musculoskeletal, 45% dermatological) in the placebo group (p = 0.11). The low density lipoprotein (LDL) cholesterol level increased significantly in the placebo but not raloxifene treated patients. No significant changes in homocysteine, hsCRP and sTM levels were observed in either group of patients. Raloxifene significantly improves lumbar spine BMD in SLE patients but does not cause an increase in lupus activity or flares.