Efficacy of 4-year denosumab treatment alone or in combination with teriparatide in Japanese postmenopausal osteoporotic women

Abstract

Purpose: This extended randomized prospective study aimed to compare the 4-year clinical outcomes of denosumab treatment alone or in combination with teriparatide in treatment-naïve postmenopausal Japanese patients with osteoporosis.

Methods: Between July 2013 and December 2016, 30 eligible women from our previous study were enrolled. After newly adding 17 randomly assigned patients, 47 patients were classified into the denosumab alone group (denosumab group, n?=?22) or denosumab plus teriparatide group (combination group, n?=?25). Serum bone-specific alkaline phosphatase (BAP), serum tartrate-resistant acid phosphatase (TRACP)-5b, urinary cross-linked N-terminal telopeptide of type I collagen (NTX), and bone mineral density (BMD) of the lumbar 1–4 vertebrae (L-BMD) and bilateral total hips (H-BMD) were determined at the first visit and at regular time points up to 48 months of treatment to determine percentage changes.

Results: BAP was significantly decreased from baseline in both groups from 24 to 48 months, with significant differences at all time points between the groups. TRACP-5b and urinary NTX were comparably decreased at every time point in both groups versus pretreatment levels. L-BMD was significantly more increased by combination therapy over denosumab alone at 24 and 30 months (21.1% increase vs. 14.2% increase at 48 months). There were no significant differences in H-BMD between the groups, although levels tended to be higher in the combination group throughout the study period (9.7% increase vs. 6.8% increase at 48 months).

Conclusion: Long-term denosumab and teriparatide combination therapy represents an effective treatment option for primary osteoporosis patients with low L-BMD.     

Effects of denosumab treatment in chronic liver disease patients with osteoporosis

BACKGROUND Effective treatment of osteoporosis is essential for improving morbidity and health-related quality of life in chronic liver disease(CLD) patients. Denosumab has been shown to increase bone mineral density(BMD) and decrease the risk of osteoporotic fracture in the general population. However, there are few reports evaluating the efficacy of denosumab in CLD patients.AIM To investigated the effects and safety of denosumab in CLD patients with osteoporosis.METHODS Sixty CLD patients with osteoporosis were subcutaneously administered denosumab once every 6 mo. The study period for evaluating efficacy and safety was 12 mo. Changes from baseline in BMD at the lumbar spine, femoral neck, and total hip were evaluated at 12 mo of denosumab treatment. Bone turnover and quality were assessed by measuring serum tartrate-resistant acid phosphatase-5 b(bone resorption marker), serum total procollagen type I N-terminal propeptide(bone formation maker), and plasma pentosidine(bone quality marker).RESULTS Among the 405 CLD patients, 138(34.1%) patients were diagnosed with osteoporosis; among these, 78 patients met the exclusion criteria and thus 60 patients were finally included in the present study. The median percentage changes from baseline to 12 mo of denosumab treatment in BMD at the lumbar spine, femoral neck, and total hip were +4.44%, +3.71%, and +4.03%, respectively. Denosumab significantly improved BMD, regardless of sex, patient age, and presence of liver cirrhosis. Serum tartrate-resistant acid phosphatase-5 b and procollagen type I N-terminal propeptide levels constantly and significantly declined after denosumab treatment(P 0.001). Plasma pentosidine levels were also significantly lower at 12 mo of treatment(P = 0.010). No patients experienced fractures and moderate-to-severe adverse events, except for transient hypocalcemia.CONCLUSION Denosumab treatment was safe and increased BMD, suppressed bone turnover, and improved bone quality marker levels in CLD patients with osteoporosis, irrespective of differences in baseline characteristics.     

Efficacy and safety of human parathyroid hormone-(1-84) in increasing bone mineral density in postmenopausal osteoporosis

Daily sc injections of N-terminal analogs of PTH increase bone mass and decrease fractures in osteoporotic women. We investigated the efficacy and safety of human PTH-(1-84) (full-length PTH) in the treatment of postmenopausal osteoporosis in a double-blind, placebo-controlled study. The women (n = 50-53/group) self-administered PTH (50, 75, or 100 microg) or placebo by daily sc injection for 12 months. PTH treatment induced time- and dose-related increases in lumbar spine bone mineral density (BMD). The 100-microg dose increased BMD significantly at 3 months (+2.0%) and 12 months (+7.8%). BMD underestimated the anabolic effect of PTH in lumbar spine (bone mineral content, +10.0%) because bone area increased significantly (+2.0%). A nonsignificant decrease (-0.9%) in total hip BMD occurred during the first 6 months with the 100-microg dose, but this trend reversed (+1.6%) during the second 6 months. Bone turnover markers increased during the first half of the study and were maintained at elevated levels during the second 6 months. Protocol compliance was excellent (95-98%), and treatment was generally safe and well tolerated. Dose-related incidences of transient hypercalcemia occurred, but only one patient (100-microg group) was withdrawn because of repeated hypercalcemia. Thus, full-length PTH was efficacious and safe over 12 months.     

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.     

Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial

OBJECTIVE: RANKL is essential for osteoclast development, activation, and survival. Denosumab is a fully human monoclonal IgG2 antibody that binds RANKL, inhibiting its activity. The aim of this multicenter, randomized, double-blind, placebo-controlled, phase II study was to evaluate the effects of denosumab on structural damage in patients with rheumatoid arthritis (RA) receiving methotrexate treatment. METHODS: RA patients received subcutaneous placebo (n = 75), denosumab 60 mg (n = 71), or denosumab 180 mg (n = 72) injections every 6 months for 12 months. The primary end point was the change from baseline in the magnetic resonance imaging (MRI) erosion score at 6 months. RESULTS: At 6 months, the increase in the MRI erosion score from baseline was lower in the 60-mg denosumab group (mean change 0.13; P = 0.118) and significantly lower in the 180-mg denosumab group (mean change 0.06; P = 0.007) than in the placebo group (mean change 1.75). A significant difference in the modified Sharp erosion score was observed as early as 6 months in the 180-mg denosumab group (P = 0.019) as compared with placebo, and at 12 months, both the 60-mg (P = 0.012) and the 180-mg (P = 0.007) denosumab groups were significantly different from the placebo group. Denosumab caused sustained suppression of markers of bone turnover. There was no evidence of an effect of denosumab on joint space narrowing or on measures of RA disease activity. Rates of adverse events were comparable between the denosumab and placebo groups. CONCLUSION: Addition of twice-yearly injections of denosumab to ongoing methotrexate treatment inhibited structural damage in patients with RA for up to 12 months, with no increase in the rates of adverse events as compared with placebo.     

Significant improvement of bone mineral density by denosumab without bisphosphonate pre-treatment in glucocorticoid-induced osteoporosis

Objective: The aim of this study was to evaluate differences in outcomes of denosumab for a year with or without bisphosphonate (BP) pre-treatment in patients with glucocorticoid-induced osteoporosis (GIO).

Methods: Forty-eight female patients with GIO and low bone mineral density (BMD) (T score of BMD; less than ?3.0 SD) were, retrospectively, enrolled and classified into the following two groups: (1) GIO with BP pre-treatment (BP pre-treated group; n?=?24) and (2) GIO without BP treatment (BP pre-untreated group; n?=?24). We measured serum bone alkaline phosphatase (BAP), N-terminal propeptide of type 1 procollagen (P1NP), and tartrate-resistant acid phosphatase (TRACP)-5b at baseline, and at 3, 6, and 12 months. We also assessed BMD of the lumbar 1–4 vertebrae BMD (L-BMD) and bilateral hip BMD (H-BMD) at baseline, and at 6 and 12 months.

Results: TRACP-5b was significantly inhibited at 3 months in both groups and at 6 and 12 months in the BP pre-untreated group compared with pre-treatment levels. Both BAP and P1NP were significantly suppressed at 3, 6, and 12 months in both groups compared with baseline values. L-BMD and H-BMD were significantly increased at 6 (4.2% and 3.4%, respectively) and 12 months (4.7% and 4.7%, respectively) in the BP pre-untreated group over pre-treatment levels. There were no significant differences between the groups during the observational period.

Conclusion: Denosumab significantly improved both L-BMD and H-BMD in the BP pre-untreated group, but not in the BP pre-treated group, suggesting it to be a good option for GIO patients without BP pre-treatment.     

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.     

Comparison of the effects of denosumab with either active vitamin D or native vitamin D on bone mineral density and bone turnover markers in postmenopausal osteoporosis

Osteoporosis is a worldwide health concern. Although treatment with denosumab plus the active vitamin D alfacalcidol has been found to improve femoral neck (FN) and distal forearm bone mineral density (BMD), there have been no reports on the efficacy or adverse effects of denosumab plus eldecalcitol (ELD) in primary osteoporosis patients. Fifty-six treatment-naïve post-menopausal women with primary osteoporosis were recruited and divided into denosumab plus native vitamin D or denosumab plus ELD. Ultimately, 26 subjects in the native vitamin D group and 24 in the ELD group were analyzed. Lumbar and total hip BMD significantly increased in both groups. However, there was no significant difference in the percent increase of lumbar and total hip BMD between two groups. FN-BMD was significantly increased from 6 to 12 months in the ELD group compared with baseline. This study revealed that combination therapy with denosumab and ELD could improve FN-BMD more effectively than denosumab plus native vitamin D. Thus, the addition of ELD may enhance the effects of denosumab treatment for primary osteoporosis.     

Denosumab‐mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients

Objective

Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores.

Methods

Patients receiving methotrexate for erosive RA were randomized in a 1:1:1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x‐ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months).

Results

There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and ?1.2% and ?2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores.

Conclusion

In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.

     

降钙素治疗老年骨质疏松症的临床研究

目的　观察鲑鱼降钙素对老年骨质疏松症的治疗效果。　方法　将经双能X线骨密度仪 (DEXA)测定确诊为骨质疏松且有临床症状的老年患者 86例分成两组 ,鲑鱼降钙素组 4 6例 ,予以鲑鱼降钙素肌肉注射 ,每天 1次 10 0IU ,连用 3d后 ,改为 5 0IU隔天 1次 ,连用 1个月 ,间歇 1个月后再重复 ,共半年 ,同时加服钙尔奇D每天 1片 ;对照组 4 0例 ,单纯口服钙尔奇D每天 1片 ,疗程半年 ,两组治疗前后均测定 1～ 4腰椎 (L1-4)及股骨近端骨密度 (BMD) ,治疗后记录临床症状。　结果　鲑鱼降钙素组较对照组骨痛症状缓解 (91 3%和 4 7 5 % )效果明显 (P <0 0 1) ,鲑鱼降钙素组腰椎BMD (0 78± 0 12 ) g/cm2 较治疗前 (0 73± 0 10 ) g/cm2 有所升高 (P <0 0 5 ) ,股骨近端BMD变化不明显 ;对照组BMD无明显改变。　结论　鲑鱼降钙素与钙剂联合对治疗老年骨质疏松患者有缓解临床症状及增加腰椎BMD的作用。     

Increased Fracture Risk Assessed by Fracture Risk Assessment Tool in Greek Patients with Crohn’s Disease

Background

The World Health Organization has recently developed the Fracture Risk Assessment Tool (FRAX) based on clinical risk factors and bone mineral density (BMD) for evaluation of the 10-year probability of a hip or a major osteoporotic fracture. The aim of this study was to evaluate the use of the FRAX tool in Greek patients with inflammatory bowel disease (IBD).

Methods

FRAX scores were applied to 134 IBD patients [68 Crohn’s disease (CD); 66 ulcerative colitis (UC)] who underwent dual-energy X-ray absorptiometry scans at the femoral neck and lumbar spine during the period 2007–2012. Calculation of the FRAX scores, with or without BMD, was made through a web-based probability model used to compute individual fracture probabilities according to specific clinical risk factors.

Results

The median 10-year probability of a major osteoporotic fracture for IBD patients based on clinical data was 7.1 %, and including the BMD was 6.2 %. A significant overestimation with the first method was found (P = 0.01). Both scores with and without BMD were significantly higher in CD patients compared with UC patients (P = 0.02 and P = 0.005, respectively). The median 10-year probability of hip fracture based on clinical data was 0.8 %, and including the BMD was 0.9 %. The score with use of BMD was significantly higher in CD compared with UC patients (P = 0.04).

Conclusions

CD patients have significantly higher FRAX scores and possibly fracture risk compared with UC patients. The clinical FRAX score alone seems to overestimate the risk of osteoporotic fracture in Greek IBD patients.     

Comparison of the efficacy of denosumab and bisphosphonates for treating secondary osteoporosis in patients with rheumatoid arthritis

Objectives: This study aimed to investigate the efficacy of denosumab (compared with that of bisphosphonates) for preventing secondary osteoporosis and inflammation caused by excessive bone resorption in Japanese rheumatoid arthritis (RA) patients never previously treated for osteoporosis.

Methods: Ninety-eight patients with coexisting RA and osteoporosis were enrolled. The patients were subdivided by whether they were treated with denosumab (n?=?49) or traditional bisphosphonates (n?=?49). RA disease activity, bone turnover markers, and bone mineral density (BMD) were compared between the two groups before treatment, and after 6 and 12 months of treatment.

Results: There was no significant difference between the groups in any of the disease activity indices and BMD at any of the measured time points. With regard to bone metabolism, denosumab significantly reduced bone-specific alkaline phosphatase at 6 and 12 months compared with pretreatment, but had no effect on tartrate-resistant acid phosphatase 5b levels, suggesting an effect on the bone formation rate, but not on the bone resorption rate.

Conclusions: Neither denosumab nor bisphosphonates could suppress inflammation or RA disease activity, but denosumab significantly suppressed a marker of bone metabolism in Japanese RA patients never previously treated for osteoporosis.     

降钙素治疗老年性骨质疏松症45例临床观察

目的　 观察降钙素对老年性骨质疏松症 (OP)的作用。　 方法 　将 80例OP病人随机分成 2组 ,降钙素组 45例 ,隔日肌注降钙素 5 0U ,每日加服碳酸钙 维生素D 0 6 ,对照组 35例 ,每日碳酸钙 维生素D 0 6 ,疗程均为 6月 ,每组用药 6月前后分别检测腰椎前后位、腰椎 3侧位右髋部骨密度 (BMD)、血清碱性磷酸酶 (ALP)、骨钙素(BGP)、酸性磷酸酶 (ACP)及尿吡啶酚 /肌酐 (Pyd/Cr)比值。　 结果 　降钙素组腰椎前后位 1～ 4及腰 3侧位BMD分别升高 11 8%、9 3 %、8 2 %、10 2 %和 10 3 % ,髋部BMD升高不明显 ,与此同时 ,血清ALP、BGP、ACP及Pyd/Cr比值明显降低 (P <0 0 5 ) ,疼痛改善。对照组用药物后无明显改变。　 结论 　小剂量降钙素能够增加老年性OP病人腰椎BMD ,其机理与抑制骨吸收 ,降低骨转换率有关。     

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.     

Higher visit-to-visit intra-dialytic blood pressure is associated with the progression of aortic valve stenosis in chronic hemodialysis patients

Aortic valve stenosis (AS) is a frequent complication contributing to poor prognosis in chronic hemodialysis (CHD) patients. High blood pressure (BP) is known to be associated with AS progression in the general population. In CHD patients, however, BP varies during and between hemodialysis sessions with ultrafiltration volume or inter-dialytic weight gain; therefore it is difficult to characterize the BP status with a conventional single measurement. Our purpose was to clarify the BP variables affecting AS progression in CHD patients. We retrospectively enrolled 32 consecutive CHD patients with AS [aortic valve area (AVA), 1.3 ± 0.3 cm²; mean age 69 ± 8 years] who had serial transthoracic echocardiographic studies at least 6 months apart (mean 23 ± 9 months). AS progression was evaluated using absolute reduction in AVA per year. Pre-dialytic and intra-dialytic (every hour during sessions) BPs throughout the 3 consecutive visits were used to determine each patient’s BP status. We calculated the mean values of pre-dialytic and intra-dialytic BPs and their variability. In univariate analysis, mean visit-to-visit pre-dialytic and intra-dialytic BP were associated with AS progression, whereas all variables of BP variability were not. Multiple regression analysis indicated that only mean visit-to-visit intra-dialytic systolic and diastolic BP remained independently associated with AS progression after adjustment for age, sex, hypertension, hypercholesterolemia, diabetes mellitus, and serum parathyroid hormone (p < 0.05). Although BP regulation in CHD patients is complex and multifactorial, mean visit-to-visit intra-dialytic BP was independently associated with AS progression. Prospective studies are necessary before considering intra-dialytic BP as a potential target for therapy.     

鲑鱼降钙素鼻喷剂治疗绝经后骨质疏松患者骨密度及骨转换指标的变化

目的 观察鼻喷鲑鱼降钙素(calcitonin)治疗绝经后骨质疏松症(postmenopausal osteoporosis,PMO)患者6个月和12个月后骨密度及骨转换指标的变化.方法 选择PMO患者共67例,给予鼻喷降钙素治疗37例;其余30例PMO患者单纯服用钙剂和维生素D作为对照组.各组分别于用药前和用药后6个月和12个月采用DEXA骨密度仪测定骨密度;定量夹心酶联免疫法(ELISA)测定Ⅰ型胶原N末端肽(NTX)、骨特异性碱性磷酸酶(BALP)、抗酒石酸酸性磷酸酶(TRACP-5b)、25-羟维生素D,化学发光法测定骨钙素(BGP).结果 5例患者因医疗费用、拒绝坚持治疗退出试验,鼻喷降钙素组共32例完成试验.鼻喷降钙素治疗6个月后可见患者股骨颈和腰椎骨密度均较前有所增加,但仅在腰椎差异有统计学意义(P＜0.05),而在股骨颈治疗前后骨密度的差异无统计学意义(P＞0.05).治疗12个月时股骨颈和腰椎骨密度较前均明显升高,差异有统计学意义(P＜0.05).对照组在治疗6个月时的腰椎和治疗12个月时的股骨颈和腰椎部位骨密度均较治疗前降低,差异有统计学意义(P＜0.05).鼻喷降钙素治疗6个月和12个月时,股骨颈和腰椎骨密度均较对照组升高(P＜0.05).鼻喷降钙素治疗6个月后,TRACP-5b、NTX/Cr较治疗前降低,差异有统计学意义(P＜0.05);治疗12个月后,除TRACP-5b、NTX/Cr较前降低更加明显以外(P＜0.01),BALP较治疗前有升高,差异有统计学意义(P＜0.05).对照组在治疗12个月时,BALP较前有降低,差异有统计学意义(P＜0.05).25-羟维生素D在各组经治疗后,均明显升高,差异有统计学意义.结论 本研究结果显示鼻喷降钙素治疗6个月有效,12个月效果显著,可预防骨丢失,增加骨量.

Abstract：

Objective To study the changes of bone mineral density(BMD)and bone turnover in postmenopausal osteoporotic patients treated with salmon calcitonin nasal spray. Methods Sixty-seven postmenopausal osteoporotic patients were enrolled in our trial. All of them received calcium and vitamin D; 37patients were treated with salmon calcitonin nasal spray for 12 months and the other 30 patients received calcium and vitamin D only. Dual-energy X-ray absorptiometry(DEXA)and measurements of a series of bone turnover indices were performed before and after medication for 6 and 12 months. Results After treatment with salmon calcitonin nasal spray for6 months, BMD in lumbar spine 2-4 increased but no change occurred in femoral neck. However, after treatment for 12 months, BMD in both lumbar spine 2-4 and femoral neck increased. In the control group, BMD in lumbar spine 2-4 decreased after treatment for 6 and 12 months, but BMD in femoral neck decreased only after 12months. Comparing with the control group, after treatment with salmon calcitonin nasal spray, BMD in lumbar spine 2-4 and femoral neck were increased obviously. The level of TRACP-5b and NTX/Cr decreased after treatment with salmon calcitonin nasal spray for6 months and 12 months, while BALP increased only after treatment for 12 months. In the control group, BALP decreased after treatment for 12 months. The level of 25-(OH)vitamin D increased after treatment for 6 months and 12 months in both groups. Conclusions Long-term treatment with salmon calcitonin nasal spray prevents bone loss and may increase bone mass.     

Intravenous zoledronic acid treatment in thalassemia-induced osteoporosis: results of a phase II clinical trial

Osteoporosis is an important cause of morbidity in beta-thalassemia patients. Bisphosphonates have been recently used for the treatment of osteoporosis in beta-thalassemia. This study is a prospective quasi-experimental study to assess the efficacy and safety of zoledronic acid in thalassemics with osteoporosis. Eighteen thalassemia patients with osteoporosis were given zoledronic acid 4 mg intravenously every 3 months over a period of 12 months. The efficacy of treatment was assessed by measuring (BMD) at the lumbar spine, femoral neck, and hip at baseline, 6, and 12 months. Z-score was used to measure the BMD. Other medical assessments included markers of bone formation and resorption (bone alkaline phosphatase (BAP), osteocalcin (OC), and urinary deoxypyridinoline), and the assessment of pain score, analgesic score, and performance score. Ten thalassemic osteoporotic patients were followed up only with serial BMDs as controls. Both groups had no significant difference with respect to age, gender, and baseline BMD. Patients taking zoledronic acid had a significant increase in their lumbar spine, femoral neck, trochanter, and total hip BMD measurements over the 12-month period. Patients in the control group did not have any significant change in BMD measurements. There was a significant change in the levels of OC and BAP over the 12-month follow-up period. There was also a significant decrease in the number of painful sites experienced by the patients. Treatment of thalassemic osteoporotic patients with zoledronic acid is very effective in increasing BMD at the lumbar spine and hip and in reducing pain; it is also well-tolerated.     

High incidence and severity of injection site reactions in the first cycle compared with subsequent cycles of subcutaneous bortezomib

Subcutaneous (sc) administration of bortezomib (Bor) has become more common than intravenous (iv) administration in the treatment of multiple myeloma (MM), because scBor results in a lower incidence and severity of peripheral neuropathy and shows efficacy equivalent to ivBor. Bor is an irritant cytotoxic agent when it extravasates from the vasculature. Therefore, it is recommended that sc injections of Bor should be delivered on a rotating basis across eight sites on the abdomen and thighs. Previously, we reported that sc injections of Bor in the abdomen caused fewer grade 2 injection site reactions (ISRs) than those in the thigh. In the present study, we recruited more patients and expanded the scale of our analysis into ISRs following treatment with 300 scBor injections in 20 patients. ISRs of ≥grade 2 were documented in 12 of 109 (11.0 %) thigh injections, but only in three of 191 (1.6 %) abdominal injections (p < 0.001). Interestingly, ISRs of ≥grade 2 occurred more frequently in the first cycle than in the second and subsequent cycles (16.3 vs. 0.91 %, p < 0.001). These results clearly indicate that closer attention should be paid to ISR management, particularly with regard to the first cycle of scBor administration in the thigh. To our knowledge, this is the first report showing that ≥grade 2 ISRs are more common in the first cycle compared with subsequent cycles of scBor in the treatment of MM.     

Serum vitamin D level and bone mineral density in premenopausal Egyptian women with fibromyalgia

Patients with fibromyalgia syndrome (FMS) have impaired mobility and therefore get less sunlight exposure, we postulated that they may be at increased risk of developing osteoporosis (OP). The aim of this study was to assess and compare serum vitamin D level and bone mineral density (BMD) value in patients with primary FMS (PFMS) and healthy controls. A total of 50 patients with PFMS participated in this case–control study, and 50 healthy females who were age-matched to the patients were used as the control group. Venous blood samples collected from all subjects were used to evaluate serum 25-hydroxyvitamin D3 (25-OHD). BMD was measured at the lumbar spine (L2–L4) anteroposterior, femoral neck and forearm by dual-energy X-ray absorptiometry. Patients with PFMS had significantly lower serum 25-OHD than controls (15.1 ± 6.1 and 18.8 ± 5.4 ng/ml, respectively, p = 0.0018). Apart from the BMD in the lumbar spine, which was significantly lower in the PFMS patients compared with controls (p = 0.0012), no significant difference was found in other measures of BMD. Compared to PFMS patients who had serum level of the 25-OHD >20 ng/ml, the patients with 25-OHD ≤20 ng/ml are more likely to have impaired short memory (46.4 vs. 13.6%, respectively, p = 0.0136), confusion (50 vs. 18.2%, respectively, p = 0.0199), mood disturbance (60.7 vs. 27.3%, respectively, p = 0.0185), sleep disturbance (53.6 vs. 22.7%, respectively, p = 0.0271), restless leg syndrome (57.1 vs. 27.3%, respectively, p = 0.0346) and palpitation (67.9 vs. 36.4%, respectively, p = 0.0265). Serum level of the 25-OHD is inversely correlated with visual analogue scale (VAS) of pain (p = 0.016), Beck score for depression (p = 0.020) and BMD at lumbar spine (p = 0.012). The lumbar BMD inversely correlated with VAS of pain (p = 0.013) and Beck score for depression (p = 0.016). This study confirmed high prevalence of hypovitaminosis D among in patients with PFMS. This study confirmed the concept that FMS is a risk factor for OP. Based on this, an early nutrition program rich in calcium and vitamin D, appropriate exercise protocols, and medical treatment should be considered in these patients in terms of preventing OP development.     

Fracture risk assessment and osteoporosis treatment disparities in 3,970 Japanese patients with rheumatoid arthritis

The aims of this study are to determine the proportion of patients at high risk for major osteoporotic and hip fractures in a Japanese cohort with rheumatoid arthritis (RA) and to determine if a care gap exists for high-risk patients. The Fracture Risk Assessment Tool (FRAX®) was administered to 3,970 Japanese patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis cohort study with (n?=?276) and without (n?=?3,694) the use of bone mineral density (BMD) measurement. The study population had a mean age of 62 years and was 84% female. Among the 1,522 patients ≥65 years of age, 661 (43%) and 1,304 (86%) were at high risk for a major osteoporotic fracture (10-year probability >20%) and hip fracture (>3%), respectively. Among patients at high risk for a major osteoporotic fracture (n?=?723), only 453 (63%) and 320 (44%) reported taking any osteoporosis medications and bisphosphonates, respectively. Among female patients with BMD measurements (n?=?262), the 10-year risk of a major osteoporotic fracture calculated with BMD was significantly higher than in those without BMD measurements (P?相似文献