Correlation between bone mineral density of different sites and lumbar disc degeneration in postmenopausal women

Osteoporosis and lumbar disc degeneration (LDD) have been common causes that make increasing patients suffer from different degrees of low back pain. At present, whether osteoporosis degenerates or protects disc is still controversial, and the correlation between hip bone mineral density (BMD) and LDD still remains unclear. Our study aims to analyze the correlation between BMD of different sites and LDD in postmenopausal women, and explore the potential pathophysiological mechanism of them.One hundred ninety-five postmenopausal female patients were enrolled and divided into osteoporosis, osteopenia, and normal bone mass groups. Their BMD and lumbar spine magnetic resonance imaging were retrospectively analyzed. Two spine surgeons were selected to assess LDD according to Pfirrmann grading system.Based on lumbar BMD, LDD of normal bone mass group was more severe than the other 2 groups in L1/2 and L2/3 segments (P < .05). Based on hip BMD, LDD of each disc from L1/2 to L5/S1 had no significant difference among the 3 groups (P > .05). Lumbar BMD (L1-L4) was positively correlated with corresponding degree of LDD (L1/2-L4/5) (P < .05), whereas there was no correlation between hip BMD and degree of LDD (P = .328).There is a positive correlation between lumbar BMD and LDD in postmenopausal women, which is more obvious in the upper lumbar spinal segments (L1, L2). However, there is no correlation between hip BMD and LDD, suggesting that in postmenopausal women with lumbar degenerative disease, hip BMD is more suitable for the diagnosis of osteoporosis.     

Alterations of bone markers in obese patients with type 2 diabetes after bariatric surgery: A meta-analysis and systemic review of randomized controlled trials and cohorts

Background:The aim of this study is to evaluate the alterations in bone mineral density and other surrogate markers for osteoporosis in obese patients with type 2 diabetes mellitus (T2DM) who received Roux-en-Y gastric bypass (RYGB) versus medical treatment as control.Methods:We searched 4 electronic databases and reference lists of relevant studies for eligible research published before December, 2019. After quality assessment, eligible studies were synthesized for relevant outcomes, including lumbar spine bone mineral density (L-spine BMD) change, total hip BMD change, osteocalcin level, C-terminal telopeptide level, and parathyroid hormone level.Results:Three randomized clinical trials and 2 observational studies concerning 307 total obese T2DM patients were included. Follow-up ranged from 12 to 60 months. Patients underwent RYGB surgery were associated with both higher L-spine BMD loss (mean difference: −2.90, 95% CI: −2.99∼−2.81, P < .00001) and total hip BMD loss (mean difference: −5.81, 95% CI: −9.22∼−2.40, P = .0008). As to biochemical markers of bone metabolism, we found significantly higher osteocalcin level in medical treatment (control) group compared with RYGB group (mean difference: 11.16, 95% CI: 8.57–13.75, P < .00001). However, higher C-terminal telopeptide level and parathyroid hormone level were noted in medical treatment group (control) compared with RYGB group (mean difference: 0.29, 95% CI: 0.11–0.48, P = .002; mean difference: 1.56, 95% CI: 0.84–2.27, P < .0001).Conclusions:RYGB surgery is associated with negative impact on bone metabolism and increase the risk of osteoporosis in obese patients with T2DM. We suggest that clinicians acknowledge the adverse effects of surgery and keep monitoring bone mineral components in post-RYGB populations. Further studies regarding the optimal amount of perioperative and postsurgical supplementation should be evaluated.     

狄诺塞麦:治疗绝经期女性骨质疏松的新希望

狄诺塞麦是目前用于治疗绝经期骨质疏松的第一种单克隆抗体药物.它能与细胞核因子-κB受体活化因子配体(RANKL)结合,通过抑制破骨细胞的产生、功能和存活,减少骨吸收达到治疗作用.临床试验显示,在绝经后骨质疏松妇女中,狄诺塞麦增加骨密度(BMD)和降低骨折风险的作用优于安慰剂和阿仑膦酸,不良反应与安慰剂和阿仑膦酸相当.药...     

The Efficacy of Parathyroid Hormone Analogues in Combination With Bisphosphonates for the Treatment of Osteoporosis: A Meta-Analysis of Randomized Controlled Trials

Parathyroid hormone (PTH) analogues increase bone strength primarily by stimulating bone formation, whereas antiresorptive drugs (bisphosphonates) reduce bone resorption. Therefore, some studies have been designed to test the hypothesis that the concurrent administration of the 2 agents would increase bone density more than the use of either one alone. This meta-analysis aimed to determine whether combining PTH analogues with bisphosphonates would be superior to PTH alone.Electronic databases were searched to identify relevant publications up to March, 2014. Randomized controlled trials (RCTs) comparing PTH analogues combined bisphosphonates with PTH for osteoporosis were analyzed. According to the Cochrane Handbook for systematic Reviews of Interventions 5.2, we identified eligible studies, evaluated the methodological quality, and abstracted relevant data.Totally 7 studies involving 641 patients were included for meta-analysis. The pooled data showed that there were no significant differences in the percent change of spine BMD (MD_1-year = −0.97, 95% CI −2.81 to 0.86, P = 0.30; MD_2-year =  − 0.57, 95% CI −5.01 to 6.14, P = 0.84), femoral neck BMD (MD_1-year = 0.60, 95% CI −0.91 to 2.10, P = 0.44; MD_2-year = −0.73, 95% CI −4.97 to 3.51, P = 0.74), the risk of vertebral fracture (risk ratio [RR] = 1.27; 95% CI 0.29–5.57; P = 0.75), and the risk of nonvertebral fracture (RR = 0.97; 95% CI 0.40–2.35; P = 0.95) between the 2 groups, whereas combination group improves the percent change of hip BMD at 1 year (MD = 1.16, 95% CI 0.56–1.76; P < 0.01) than PTH analogues group.Our results showed that there was no evidence for the superiority of combination therapy, although significant change was found for hip BMD at 1 year in combination group. Further large multicenter randomized controlled trials are still needed to investigate the efficacy of combination therapy.     

The impact of plant-based diets on female bone mineral density: Evidence based on seventeen studies

Background:An increase in awareness of plant-based diets has brought forth numerous studies on bone mineral density (BMD). The present systematic review and meta-analysis was designed to compare the effect between plant-based diets and omnivores on female BMD.Methods:We searched the Cochrane Library, PubMed, EMBASE, and Web of Science and up to July 1, 2020. Mean difference (MD) with its 95% confidence interval (CI) was estimated to compare the outcomes of the groups. We compared BMD at the lumbar spine, femoral neck and whole body respectively between plant-based diets and omnivores. In addition, we performed subgroup analyses according to different clinical characteristics for further exploration. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2.Results:A total of 17 cross-sectional studies including 13,888 patients were identified for the present meta-analysis. Our pooled result indicated that population with plant-based diets had lower BMD than omnivores at the lumbar spine (MD −0.03; 95% CI −0.04 to −0.02; P < .0001), femoral neck (MD −0.04; 95% CI −0.05 to −0.03; P < .00001) and whole body (MD −0.04; 95% CI −0.06 to −0.01; P = .01), respectively. Further exploration indicated that especially females with plant-based diets experienced significantly lower BMD at lumbar spine (MD −0.03; 95% CI −0.04 to −0.02; 3173 pts), femoral neck (MD −0.04; 95% CI −0.05 to −0.03; 10,656 pts) and whole body (MD −0.05; 95% CI −0.10 to −0.00; P = .04). In addition, we performed subgroup analyses and found lower BMD at lumbar spine and femoral neck in both vegetarians and vegans.Conclusions:The present meta-analysis indicated that plant-based diets may be correlated with lower BMD of women when compared with omnivore population. However, this does not diminish the fact that a plant-based diet can be a harmful option to the overall bone health of population and more prospective researches are needed to clear the impact of plant-based diets on bone health.     

Denosumab for joints and bones

Denosumab is an investigational, fully human monoclonal antibody with a high affinity and specificity for receptor activator of nuclear factor κ B ligand (RANKL), a cytokine member of the tumor necrosis factor family. RANKL, an essential mediator of osteoclast formation, function, and survival, plays a major role in the pathogenesis of postmenopausal osteoporosis, structural damage in rheumatoid arthritis, and bone loss associated with other skeletal disorders. Denosumab suppresses bone turnover by inhibiting the action of RANKL on osteoclasts. Denosumab reduces bone turnover and increases bone mineral density in postmenopausal women with low bone mineral density, reduces fracture risk in women with postmenopausal osteoporosis, and inhibits structural damage in patients with rheumatoid arthritis when added to ongoing methotrexate treatment. It is generally well tolerated, with a good safety profile. Adverse and serious adverse events, including infections and malignancy, are similar in patients treated with denosumab or placebo.     

Diagnostic value of calcaneal quantitative ultrasound in the evaluation of osteoporosis in middle-aged and elderly patients

To study the correlation between calcaneal quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA), and analyze the diagnostic value of calcaneal QUS in the evaluation of middle-aged and elderly osteoporosis.We assessed bone mineral density (BMD) at the femoral neck and intertrochanteric of left hip and lumbar spine (L1–L4) sites with DXA and QUS parameters of the right and left calcanei in a cohort of 82 patients over the age of 50 years. Using DXA parameters as the gold standard for the diagnosis of osteoporosis, the correlation coefficient between BMD and QUS parameters was calculated. Receiver operating characteristic curve was generated and areas under the curves were evaluated. Cut-off values for QUS were defined.In men, there was a moderate correlation between calcaneal QUS and proximal femoral BMD (P < .05), but no significant correlation between calcaneal QUS and lumbar BMD (P > .05). In women, calcaneal QUS were moderately correlated with lumbar spine and proximal femoral BMD (P < .05). Using DXA as the gold standard, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of calcaneal QUS in the diagnosis of osteoporosis were 90.2%, 89.2%, 100%, 100%, and 50.0%, respectively. According to the receiver operating characteristic curve, when the QUS T-score of calcaneum was –1.8, the area under the curve was 0.888, the sensitivity was 73.21%, and the specificity was 92.31% (P < .05). When the QUS T-score of calcaneum was –2.35, the sensitivity was 37.2% and the specificity was 100%.Calcaneal QUS can be used to predict proximal femoral BMD in middle-aged and elderly people, as well as lumbar BMD in women. As a screening method for osteoporosis, calcaneal QUS has good specificity, so it can be recommended to use it as a pre-screening tool to reduce the number of DXA screening. When the QUS T-score of calcaneum is –1.8, it has the greatest diagnostic efficiency for osteoporosis; when the QUS T-score of calcaneum is ≤–2.35, it can be diagnosed as osteoporosis.     

Efficacy and Safety of Bisphosphonates for Low Bone Mineral Density After Kidney Transplantation: A Meta-Analysis

In patients with low bone mineral density (BMD) after kidney transplantation, the role of bisphosphonates remains unclear. We performed a systematic review and meta-analysis to investigate the efficacy and safety of bisphosphonates.We retrieved trials from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception through May 2015. Only randomized controlled trials that compared bisphosphonate-treated and control groups of patients with low bone mineral density after kidney transplantation were included. The primary outcomes were the percent change in BMD, the absolute change in BMD, and the BMD at the end of study at the lumbar spine. The results were expressed as the mean difference (MD) or relative risk (RR) with the 95% confidence interval (CI). We used a random-effects model to pool the outcomes.We included 17 randomized controlled trials with 1067 patients. Only 1 included trial was found to be at low risk of bias. The rest of the included studies were found to have high to uncertain risk of bias. Compared with the control group, those who received bisphosphonates had a significant increase in percent change in BMD (mean difference [MD] = 5.51, 95% confidence interval [CI] 3.22–7.79, P < 0.00001) and absolute change in BMD (MD = 0.05, 95% CI 0.04–0.05, P < 0.00001), but a nonsignificant increase in BMD at the end of the study (MD = 0.02, 95% CI −0.01 to 0.05, P = 0.25) at the lumbar spine. Bisphosphonates resulted in a significant improvement in percent change in BMD (MD = 4.95, 95% CI 2.57–7.33, P < 0.0001), but a nonsignificant improvement in absolute change in BMD (MD = 0.03, 95% CI −0.00 to 0.06, P = 0.07) and BMD at the end of the study (MD = −0.01, 95% CI −0.04 to 0.02, P = 0.40) at the femoral neck. No significant differences were found in vertebral fractures, nonvertebral fractures, adverse events, and gastrointestinal adverse events.Bisphosphonates appear to have a beneficial effect on BMD at the lumbar spine and do not significantly decrease fracture events in recipients. However, the results should be interpreted cautiously due to the lack of robustness and the heterogeneity among studies.     

The Effect of the Modified Eighth Section of Eight-Section Brocade on Osteoporosis in Postmenopausal Women: A Prospective Randomized Trial

Osteoporosis and related fragility fractures represent a serious and global public health problem.To evaluate whether the modified eighth section of Eight-section Brocade (MESE) exercise could improve the symptom and indexes associated with osteoporosis in postmenopausal women.Guangzhou and Liuzhou hospital of traditional Chinese medicine in China.Women (n = 198) aged 50 to 75 years were randomized into Control, Ca, MESE, and MESE + Ca.Subjects in Ca and MESE groups were separately asked to consume thrice daily Calcium Carbonate Chewable D3 tablet and to perform thrice daily MESE exercise by 7 repetitions per time for 12 months. Subjects in MESE + Ca group performed such the combined treatment project for 12 months. Body height and Hospital for Special Surgery (HSS) scores of both knees, chronic back pain visual analogue scale scores (VAS), bone mineral density (BMD) at L2 to L4 and the left femoral neck, 3-feet Up and Go Test (3′) and one-leg Stance (OLS).In our study, the improvement in chronic back pain of the patients in Ca, MESE, and MESE + Ca group was better than that in control group. There was 1.9% and 1.7%, 2.3%, and 2.1% net profit in left femoral neck and lumbar BMD after the treatment for 12 months in MESE and MESE + Ca groups. For the balance capacity, the subjects in MESE and MESE + Ca groups secured much better performance than those in Ca and control group after the treatment for 12 months (P < 0.001, P < 0.001).The treatment of MESE exercise is the most effective for the improvement of the symptom and indexes in postmenopausal women. Importantly, the low attrition and the high exercise compliance indicate that MESE exercise is safe, feasible, and well tolerated by postmenopausal women.     

Effects of denosumab on bone mineral density and bone turnover in postmenopausal women

CONTEXT: Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, a mediator of osteoclastogenesis and osteoclast survival. OBJECTIVE: This study evaluated the ability of denosumab to increase bone mineral density (BMD) and decrease bone turnover markers (BTMs) in early and later postmenopausal women with low BMD. DESIGN AND SETTING: This 2-yr randomized, double-blind, placebo-controlled study was conducted in North America. PARTICIPANTS: Subjects included 332 postmenopausal women with lumbar spine BMD T-scores between -1.0 and -2.5. Interventions: SUBJECTS were randomly assigned to receive denosumab sc, 60 mg every 6 months, or placebo. Randomization was stratified by time since onset of menopause (< or =5 yr or > 5 yr). MAIN OUTCOME MEASURES: The primary end point was the percent change in lumbar spine BMD by dual-energy x-ray absorptiometry at 24 months. Additional end points were percent change in volumetric BMD of the distal radius by quantitative computed tomography; percent change in BMD by dual-energy x-ray absorptiometry for the total hip, one-third radius, and total body; hip structural analysis; percent change in BTMs; and safety. RESULTS: Denosumab significantly increased lumbar spine BMD, compared with placebo at 24 months (6.5 vs. -0.6%; P<0.0001) with similar results for both strata. Denosumab also produced significant increases in BMD at the total hip, one-third radius, and total body (P < 0.0001 vs. placebo); increased distal radius volumetric BMD (P < 0.01); improved hip structural analysis parameters; and significantly suppressed serum C-telopeptide, tartrate-resistant acid phosphatase-5b, and intact N-terminal propeptide of type 1 procollagen. The overall incidence of adverse events was similar between both study groups. CONCLUSIONS: Twice-yearly denosumab increased BMD and decreased BTMs in early and later postmenopausal women.     

Denosumab for the treatment of osteoporosis: A systematic literature review

PurposeTo determine the efficacy and safety of denosumab in osteoporosis.MethodsA systematic search was performed in MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials (1950 to July 2010), meeting abstracts (2009–2010), trial registries, and reference lists. The selection criteria were as follows: (population) osteoporosis patients of any age; (intervention) treatment with denosumab; (outcome) efficacy and safety; (study design) randomized clinical trials (RCTs); no language restrictions. Two reviewers independently screened titles and abstracts and subsequently extracted data from the selected studies including quality items, and on outcomes of interest. A meta-analysis was performed for safety issues.ResultsA total of 25 studies were included. Denosumab reduces the risk of new radiographic vertebral fracture in a 68% compared with placebo (p < 0.001) and increases bone mineral density (BMD) at lumbar spine, total hip, and one-third radius more than alendronate and placebo. A single subcutaneous dose of denosumab resulted in a dose-dependent, rapid, profound, and sustained decrease bone turnover markers (BTMs). Denosumab was in general well tolerated. A meta-analysis has shown an increase in the incidence of urinary infections (p = 0.012) and eczema (p < 0.001) in the patients treated with denosumab. Meta-analysis of efficacy was complicated due to the study features.ConclusionsDenosumab given subcutaneously twice yearly is associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. Denosumab is associated with greater and sustained increases in BMD and reductions in BTMs compared with placebo and/or alendronate and with a risk of urinary infections and eczema.     

Comparison of the effect of alendronate on lumbar bone mineral density and bone turnover in men and postmenopausal women with osteoporosis

The purpose of the present study was to compare the effect of alendronate treatment on lumbar bone mineral density (BMD) and bone turnover in men and postmenopausal women with osteoporosis. Sixty men with primary or secondary osteoporosis and 318 women with postmenopausal osteoporosis were treated with alendronate. The primary end points were lumbar BMD and urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels. The secondary end point was the incidence of vertebral and nonvertebral fractures. Forty-seven (78.3%) men and 254 (79.9%) women who could complete the 12-month trial were analyzed. The mean ages of men and postmenopausal women were 69.1 and 70.4 years, respectively. Both men and postmenopausal women showed higher levels of urinary NTX as compared with normal range of premenopausal women. Alendronate treatment decreased urinary NTX level by 39.2% in men and 45.4% in postmenopausal women at 3 months and serum ALP level by 17.8 and 21.0%, respectively, at 12 months. Following reduction in bone turnover markers, lumbar BMD increased 5.8 and 7.6% in men and postmenopausal women, respectively, at 12 months. Reduction in urinary NTX level and increase in lumbar BMD were smaller in men than in postmenopausal women. The incidence of vertebral and nonvertebral fractures was 10.6 and 8.5%, respectively, in men and 8.3 and 7.5%, respectively, in postmenopausal women, with no significant difference in these incidences between them. These results suggested that alendronate treatment effectively increased lumbar BMD from baseline in men with primary or secondary osteoporosis following reduction in bone turnover, although its efficacy did not appear to be greater than in postmenopausal women with osteoporosis. We have no funding sources; we have no conflict of interest.     

Is addition of sodium fluoride to cyclical etidronate beneficial in the treatment of corticosteroid induced osteoporosis?

OBJECTIVE—To investigate whether administration of sodium fluoride (NaF) in addition to cyclical etidronate has a positive effect on bone mineral density (BMD) in patients with established osteoporosis during continued treatment with corticosteroids.
PATIENTS AND METHODS—47 patients who were receiving treatment with corticosteroids were included in a two year randomised, double blind, placebo controlled trial. Established osteoporosis was defined as a history of a peripheral fracture or a vertebral deformity, or both, on a radiograph. All patients were treated with cyclical etidronate, calcium, and either NaF (25 twice daily) or placebo. Vitamin D was supplemented in the case of a low serum 25 (OH) vitamin D concentration. BMD of the lumbar spine and hips was measured at baseline and at 6, 12, 18, and 24 months.
RESULTS—After two years of treatment, the BMD of the lumbar spine in the etidronate/NaF group had increased by +9.3% (95% confidence intervals (CI): +2.3% to +16.2%, p<0.01), while the BMD in the etidronate/placebo group was unchanged: +0.3% (95% CI: −2.2% to +2.8%). The difference in the change in BMD between groups was +8.9% (95% CI: +1.9% to +16.0%, p<0.01). For the hips, no significant changes in BMD were observed in the etidronate/NaF group after two years: −2.5% (95% CI: −6.8% to +1.8%); in the etidronate/placebo group BMD had significantly decreased: −4.0% (95% CI: −6.6% to −1.4%; p<0.01). The difference between the groups was not significant: +1.5% (95% CI: −3.4% to +6.4%). No significant differences in number of vertebral deformities and peripheral fractures were observed between the two groups.
CONCLUSION—The effect of combination treatment with NaF and etidronate on the BMD of the lumbar spine in corticosteroid treated patients with established osteoporosis is superior to that of etidronate alone.

     

Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women

This study compared the effects of oral alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. Women at least 5 yr postmenopause (n = 299) were randomized to either 10 mg alendronate, matching alendronate placebo, or open-label intranasal calcitonin 200 IU daily for 12 months. Hip and spine bone mineral density (BMD) and markers of bone turnover were measured, and safety and tolerability were assessed. Alendronate produced greater increases in BMD than calcitonin at 12 months at the lumbar spine (5.16% vs. 1.18%; P < 0.001), trochanter (4.73% vs. 0.47%; P < 0.001), and femoral neck (2.78% vs. 0.58%; P < 0.001). Changes in BMD with calcitonin were greater than with placebo at the femoral neck, but were not different from placebo at either the trochanter or lumbar spine. Greater decreases in bone turnover were seen with alendronate than with calcitonin (serum bone-specific alkaline phosphatase, 43% vs. 9%, P < 0.001; urinary N-telopeptide, 62% vs. 11%, P < 0.001). Similar percentages of patients in each group reported an adverse experience during the study. We conclude that, in postmenopausal women with osteoporosis, 12 months of therapy with alendronate produced significantly greater increases in BMD of the hip and spine and greater decreases in bone turnover than intranasal calcitonin.     

Strontium ranelate: a novel treatment for postmenopausal osteoporosis: a review of safety and efficacy

Strontium ranelate is a new orally administered agent for the treatment of women with postmenopausal osteoporosis that reduces the risk of vertebral and hip fractures. Evidence for the safety and efficacy of strontium ranelate comes from two large multinational trials, the SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment Of Postmenopausal Osteoporosis) studies. The SOTI study evaluated vertebral fracture prevention in 1649 postmenopausal women with a mean age of 69 y. The subjects all had at least one previous vertebral fracture and a low spine bone mineral density (BMD) (equivalent to a Hologic spine T-score below −1.9). The strontium ranelate group had a 41% lower risk of a new vertebral fracture than the placebo group over the three-year study period (relative risk [RR]=0.59; 95% confidence interval [CI]: 0.48–0.73; p<0.001). The TROPOS study evaluated non-vertebral fracture prevention in 5091 postmenopausal women with a mean age of 77 y. The subjects were aged 74 y and over (or 70–74 y with one additional risk factor) and a low femoral neck BMD (equivalent to an NHANES III [Third National Health and Nutrition Examination Survey] T-score below −2.2). Over the three-year study period there was a 16% reduction in all non-vertebral fractures (RR=0.84; 95% CI 0.702–0.995; p=0.04) and a 19% reduction at the principal sites for non-vertebral fractures. The TROPOS study was not powered to investigate hip fracture risk. However, in a high risk group of women aged 74 y and over and with an NHANES III femoral neck T-score less than −2.4 there was a 36% reduction in hip fracture risk (RR=0.64; 95% CI: 0.412–0.997; p=0.046). The overall incidence of adverse events did not differ significantly from placebo and were generally mild and transient, the most common being nausea and diarrhea. Strontium ranelate is a useful addition to the range of anti-fracture treatments available for treating postmenopausal women with osteoporosis and is the only treatment proven to be effective at preventing both vertebral and hip fractures in women aged 80 y and over.     

Dose-Effectiveness Relationships Determining the Efficacy of Ibandronate for Management of Osteoporosis: A Meta-Analysis

The purpose of this study was to perform a meta-analysis on the efficacy of ibandronate by evaluating the effect sizes of different dosing regimens.Major electronic databases were searched from 1985 to February 2015. A random effects meta-analysis was performed in STATA.Data from 34 studies (13,639 patients) were included in this meta-analysis. Ibandronate treatment significantly improved lumbar spine bone mineral density (BMD) as shown by the percent change from baseline (4.80%, P < 0.0001, 95% confidence interval [CI] [4.14, 5.45]). The respective effect sizes for oral intake and intravenous (IV) infusion were 4.57% and 5.22% (P < 0.0001, CIs [3.71, 5.42] and [4.37, 6.07]), respectively. All doses led to a significant increase in BMD except 2 oral dose regimens (1 mg/d: 4.65%, P = 0.285, 95% CI [−3.87, 13.18] and 0.5 mg/d: 3.60%, P = 0.38, 95% CI [−4.43, 11.64]. Ibandronate treatment (overall as well as dose wise) also significantly improved the total hip BMD—2.30% overall, 2.13% oral, and 2.63% IV (P < 0.0001, 95% CIs [1.96, 2.64], [1.70, 2.55], and [2.07, 3.20]), respectively. Ibandronate administration significantly decreased serum markers of bone resorption to −46.53% for C-terminal telopeptide of type 1 collagen, −24.03% for bone-specific alkaline phosphatase, and −50.17% for procollagen type I N-terminal propeptide (P < 0.0001, 95% CIs [−53.16, −39.91], [−31.28, −16.77], and [−64.13, −36.20]), respectively. Parathyroid hormone levels remained unaffected by ibandronate treatment (3.03%, P = 0.439, 95% CI [−5.06, 11.66]).There was no significant difference in the efficacy of ibandronate between oral or IV administration. Predominant dose regimens for IV administration were 1 to 3 mg/3 mo and 150 mg/mo oral and 2.5 mg/d for oral ibandronate treatment.     

Efficacy of Denosumab for Osteoporosis in Patients with Rheumatic Diseases

Objective Denosumab, an anti-RANKL monoclonal antibody, was reported to improve bone mineral density (BMD) and reduce fracture risk, offering favorable efficacy against postmenopausal osteoporosis. However, some patients have experienced a reduced BMD despite denosumab therapy. Methods We performed an observational study to clarify the clinical efficacy of denosumab for osteoporosis in rheumatic disease patients. Serum levels of bone turnover markers and lumber BMD in 100 rheumatic disease patients were examined at baseline and 6 and 12 months after denosumab therapy. The independent influence of changes in the BMD was examined by multiple regression analyses adjusted for patient characteristics and bone turnover markers. Results As bone resorption markers, serum levels of N-telopeptide crosslinked of type I collagen (NTx) and tartrate-resistant acid phosphatase isoform 5b were statistically decreased after 12 months. As bone formation markers, serum levels of osteocalcin, procollagen type I N-terminal peptide, and bone alkaline phosphatase were significantly decreased after 12 months. The mean BMD was significantly increased after 12 months. However, in 10 patients, the BMD decreased. A multivariate analysis of factors related to BMD changes highlighted a young age, low prednisolone dosage, and reduction in NTx. Conclusions Denosumab increases the BMD to combat osteoporosis in rheumatic disease patients, and potential predictors of a better response to denosumab include a young age, reduction in bone turnover markers, and low-dose glucocorticoid use.     

Sex-related differences in bone metabolism in osteoporosis observational study

Although the incidence is lower in men than women, osteoporosis remains a significant health issue in men as it may give rise to severe complications if not managed appropriately. As men and women show different biological and social backgrounds, we retrospectively evaluated the differences in the bone metabolism between men and women using bone biomarkers.Bone mineral density (BMD) was determined in all patients using dual-energy X-ray absorptiometry (DXA) and analyzing various bone biomarkers such as carboxyl-terminal collagen crosslinks (CTX), osteocalcin (OCT), and alkaline phosphatase (ALP). The CTX/OCT ratio was used to estimate the association between bone absorption and formation.OCT, CTX, and ALP levels were elevated in patients with osteoporosis. Women displayed a higher incidence of osteoporosis and greater reduction in BMD than men. The mean OCT level in men was lower than that in women. Moreover, men showed significantly lower OCT levels than women of aged 65 and under 80 years old. Among patients with osteoporosis, men had a higher ratio of bone markers than women.Levels of biomarkers of bone formation and absorption were increased in the osteoporosis group. However, men showed lower increases in bone formation biomarkers than did women, indicating that the rate of bone formation relative to bone absorption did not increase in men compared with that in women. Therefore, we suggest that men and women have different bone metabolism in old age.     

Alendronate produces greater effects than raloxifene on bone density and bone turnover in postmenopausal women with low bone density: results of EFFECT (Efficacy of FOSAMAX versus EVISTA Comparison Trial) International

OBJECTIVES: Alendronate and raloxifene are antiresorptive agents with different mechanisms of action, each used to treat osteoporosis in postmenopausal women. This study was undertaken to compare the efficacy and tolerability of alendronate to raloxifene in postmenopausal women with low-bone density. DESIGN: Randomized, double-masked, double-dummy multicentre international study. SETTING: Clinical trial centres in Europe, South America and Asia-Pacific. SUBJECTS: A total of 487 postmenopausal women with low bone density, based on bone mineral density (BMD) of the lumbar spine or hip (T-score < or =-2.0). Interventions. Patients received either alendronate 70 mg once weekly and daily placebo identical to raloxifene or raloxifene 60 mg daily and weekly placebo identical to alendronate for 12 months. MAIN OUTCOME MEASURES: Evaluations included BMD of the lumbar spine and hip and markers of bone turnover at 6 and 12 months and adverse event reporting. RESULTS: Alendronate demonstrated substantially greater increases in BMD than raloxifene at both lumbar spine and hip sites at 12 months. Lumbar spine BMD increased 4.8% with alendronate vs. 2.2% with raloxifene (P < 0.001). The increase in total hip BMD was 2.3% with alendronate vs. 0.8% with raloxifene (P < 0.001). Reductions in bone turnover were significantly larger with alendronate than raloxifene. Overall tolerability was similar, however, the proportion of patients reporting vasomotor events was significantly higher with raloxifene (9.5%) than with alendronate (3.7%, P = 0.010). The proportion of patients reporting gastrointestinal events was similar between groups. CONCLUSION: In postmenopausal women with low bone density, improvements in BMD and markers of bone turnover were substantially greater during treatment with alendronate compared to raloxifene.     

A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density

Context: Men with low bone mineral density (BMD) were treated with denosumab. Objective: Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment. Design, Subjects, and Intervention: This was a placebo-controlled, phase 3 study to investigate the efficacy and safety of denosumab 60 mg every 6 months vs. placebo in men with low BMD. Main Outcome Measure: The primary endpoint was the percent change from baseline in lumbar spine (LS) BMD at month 12. Results: Of the 242 randomized subjects (mean age 65 yr), 228 (94.2%) completed 1 yr of denosumab therapy. After 12 months, denosumab resulted in BMD increases of 5.7% at the LS, 2.4% at the total hip, 2.1% at the femoral neck, 3.1% at the trochanter, and 0.6% at the one third radius (adjusted P ≤ 0.0144 for BMD percent differences at all sites compared with placebo). Sensitivity analyses done by controlling for baseline covariates (such as baseline testosterone levels, BMD T-scores, and 10-yr osteoporotic fracture risk) demonstrated that the results of the primary endpoint were robust. Subgroup analyses indicate that treatment with denosumab was effective across a spectrum of clinical situations. Treatment with denosumab significantly reduced serum CTX levels at d 15 (adjusted P < 0.0001). The incidence of adverse events was similar between groups. Conclusions: One year of denosumab therapy in men with low BMD was well tolerated and resulted in a reduction in bone resorption and significant increases in BMD at all skeletal sites assessed.