Full length parathyroid hormone,PTH(1-84), for the treatment of severe osteoporosis in postmenopausal women

ABSTRACT

Objective: To review and analyse the evidence supporting the use of full length parathyroid hormone, PTH(1-84), in the treatment of osteoporosis based on a search of several literature sources; articles selected for review were published between 1990 and 2008.

Background: PTH(1-84) is approved for the treatment of osteoporosis in postmenopausal women at high risk of fracture in Europe. It was well tolerated in clinical trials and demonstrated bone building properties and fracture prevention particularly for the lumbar spine in the treatment of postmenopausal women.

Results: The TOP clinical trial showed that PTH(1-84) treatment for 18 months resulted in a 61% reduction (p = 0.001) in new vertebral fracture incidence when compared with placebo and reduced the risk of a first vertebral fracture by 68% (p = 0.006) in women without a prevalent fracture at baseline. PTH(1-84) increased bone mineral density (BMD) at vertebral and non-vertebral sites the lumbar spine BMD increasing regardless of T-score, age, prior osteoporosis therapy or number of years post-menopause. The PaTH study showed that treatment with PTH(1-84) for 12 months increased BMD at the trabecular spine and hip. Lumbar spine BMD gains were largest with sequential administration of PTH(1-84) followed by alendronate but were smaller with concurrent administration involving anabolic and antiresorptive agents. Lumbar spine BMD increases were also seen in trials involving PTH with raloxifene and PTH in combination with hormone replacement therapy.

Conclusions: PTH(1-84) has demonstrated effective bone building qualities and extends the therapeutic options available to osteoporotic women. The use of PTH(1-84) followed by sequential administration of an antiresorptive has proved effective at increasing trabecular BMD and points towards new treatment regimens offering improvements in BMD and fracture prevention.     

Comparison of change in bone resorption and bone mineral density with once-weekly alendronate and daily risedronate: a randomised,placebo-controlled study

SUMMARY

Objective: To compare the effects of alendronate (ALN) 70mg once weekly (OW) and risedronate (RIS) 5mg daily between-meal dosing on biochemical markers of bone turnover and bone mineral density (BMD) in postmenopausal women with osteoporosis.

Research design and methods: This was a 3-month, randomised, double-blind, placebo-controlled study with a double-blind extension to 12 months. The study enrolled 549 postmenopausal women (ALN 219, RIS 222 and placebo (PBO) 108) who were >60 years of age at outpatient centres.

Main outcome measures: The primary endpoint was reduction in urine N-telopeptides of type 1 collagen (NTx) corrected for creatinine level at 3 months. Secondary parameters included change in BMD at the spine and hip at 6 and 12 months, NTx at 1,6 and 12 months, and serum bone-specific alkaline phosphatase (BSAP) at 1, 3, 6 and 12 months. Adverse experiences (AEs) were recorded throughout the study for an assessment of treatment safety profiles and tolerability.

Results: Over 3 months, ALN produced a significantly greater mean reduction in urine NTx than did RIS (?52% vs ?32%, p?<?0.001), which was maintained at 12 months. ALN produced a significantly greater mean BMD increase than did RIS at 6 months, and it was maintained at 12 months at the lumbar spine (4.8% vs 2.8%, p?<?0.001) and total hip (2.7% vs 0.9%, p?<?0.001), as well as at the trochanter and femoral neck. Significant reductions in BSAP with ALN compared to RIS were maintained over the 12 months of treatment. Study size did not allow for meaningful assessment of differences in fracture rates. Tolerability was generally similar between ALN, RIS and PBO, and the incidence of upper GIAEs causing discontinuation and oesophageal AEs was similar in the ALN and RIS groups.

Conclusion: In this study, ALN 70?mg OW produced a 50% greater reduction in bone resorption as measured by urine NTx and significantly greater increases in lumbar spine and hip BMD than did RIS 5?mg daily. The treatments had similar safety profiles and were generally well-tolerated. Additional studies are needed comparing OW ALN with OW RIS, which became available after the commencement of the present study.     

A comparison of teriparatide and calcitonin therapy in postmenopausal Asian women with osteoporosis: a 6‐month study

ABSTRACT

Objective: The number of hip fractures is expected to double in the next 20 years, with current estimates that Asia will account for 37% of these cases. As bone mineral density (BMD) may be used as a measure of fracture risk, we sought to compare the effects of teriparatide with salmon calcitonin treatment on changes in BMD, biochemical bone markers, and safety in postmenopausal Asian women with osteoporosis.

Methodology: A total of 104 patients (?n = 47 teriparatide [20?µg/day subcutaneously] and n = 57 calcitonin [100?IU/day subcutaneously]) were enrolled in Hong Kong, Singapore, Philippines, Malaysia, and Thailand. Calcium (≥ 500?mg/day) and vitamin D (200–400?IU/day) supplements were taken throughout the 6‐month controlled, randomized study.

Results: Teriparatide was associated with a 5.03 ± 4.77% increase in lumbar spine BMD (?p < 0.0001, mean ± SD change from baseline), whereas changes in lumbar spine BMD for patients on calcitonin were not statistically significant (mean change of 0.36 ± 4.12%, p = 0.16). Comparison of the two groups indicated that teriparatide treatment improved lumbar spine BMD statistically significantly more than calcitonin (?p < 0.0001). No statistically significant changes were observed for total hip or femoral neck BMD. Serum bone-specific alkaline phosphatase (BSAP) increased by 55.9% (median change from baseline, p < 0.0001) in the teriparatide group, and remained stable with calcitonin (5.0% change, p = 0.24); osteocalcin increased by 156.15% (median change from baseline, p < 0.0001) with teriparatide, and decreased with calcitonin (–15.25%, p = 0.03). Similar rates of adverse events were observed, with nausea and dizziness the most commonly reported for both groups (teriparatide versus calcitonin, 13.0% versus 23.2% p = 0.21, 10.9% versus 21.4% p = 0.19, respectively). There were no clinically relevant changes observed in laboratory parameters.

Conclusions: Both treatments were similarly tolerated, however teriparatide was associated with greater increases in lumbar spine BMD and bone formation markers, demonstrating the unique mechanism of action and safety of this treatment for osteoporosis in these Asian women.     

A randomized,double-blind,placebo-controlled study of once weekly elcatonin in primary postmenopausal osteoporosis

Objective: Very few reports have described changes in bone mineral density (BMD) with long-term, once weekly administration of elcatonin, and its effects in reducing incident fractures remain unverified. Therefore, the efficacy and safety of once weekly elcatonin were examined over a 3?year period.

Methods: This was a multicenter, double-blinded, randomized, placebo-controlled study. Postmenopausal women with primary osteoporosis received either 20?units of elcatonin (EL group, n?=?433) or placebo (P group, n?=?436) once a week for 144?weeks (3?years) intramuscularly. The primary endpoint was the incidence of new vertebral fractures at 24, 48, 72, 96, 120, and 144?weeks after the start. Secondary endpoints were the incidence of non-vertebral fractures, changes in lumbar, hip total and femoral neck BMD, and the incidence of adverse drug reactions (ADRs).

Results: No significant reduction in the incidence of new vertebral fractures was found in the EL group. The percentage increase in lumbar BMD was significantly higher in the EL group from 24?weeks to the last administration. Although the EL group showed tendencies toward smaller decreased hip total and femoral neck BMD, no significant differences were observed between groups. The incidence of ADRs was significantly greater in the EL group, although these have all been previously reported and no new safety concerns were identified.

Conclusions: Once weekly injection of 20?units of elcatonin significantly increased lumbar BMD over a 3?year period and did not cause any safety problems, but no significant reduction in the incidence of vertebral or non-vertebral fractures was demonstrated.     

Health-economic comparison of three recommended drugs for the treatment of osteoporosis

Osteoporosis is a large and growing disease with significant health consequences. Based on an evaluation of clinical evidence, the German osteology umbrella organization DVO (Dachverband Osteologie deutschsprachiger wissenschaftlicher Fachgesellschaften) published guidelines in March 2003 for the diagnosis and treatment of osteoporosis. For prevention of fractures in women with postmenopausal and senile osteoporosis, these guidelines recommend three treatment options as first-line therapy: risedronate, alendronate and raloxifene. No evidence is currently available for the reduction of hip fractures by raloxifene. Only risedronate and alendronate, therefore, are recommended for prevention of hip fractures. Information on the cost-effectiveness of preventing and treating osteoporosis may support decision makers in more efficient allocation of resources. Accordingly, the objective of this study is the comparative assessment of the cost-effectiveness of risedronate, alendronate and raloxifene for patient populations in Germany at high risk of osteoporotic fracture due to low bone mineral density (BMD) (i.e., T-score < -2.5) and resulting from a history of at least one previous vertebral fracture, as compared to osteoporotic patients with no treatment. Target variables for the economic comparison are costs per hip fracture avoided and costs per quality-adjusted life year (QALY) gained. Hip fractures are the most costly and best-documented complication of osteoporosis. A cost-effectiveness analysis was therefore conducted, using as criteria for evaluating intervention the incremental cost per hip fracture avoided and the cost per QALY gained. We used a fracture-incidence-based Markov model of osteoporosis, with analysis of patients' transition across outcome states over time (e.g., fracture, healthy, dead). Base-case analysis was conducted on a cohort of 1,000 women aged 70 with low spine BMD and prevalent vertebral fracture, over 3 years of treatment with risedronate, alendronate or raloxifene, and with application of a 10-year analytic time horizon. Model inputs included hip and vertebral fracture incidence rates; relative risk of fracture given low BMD and prevalent vertebral fracture, fracture cost, treatment prices/day (risedronate: 35 mg, 1.76 euro; alendronate: 70 mg, 1.82 euro; raloxifene: 60 mg, 1.82 euro); health utility; and efficacy in terms of relative-risk reduction of fracture of the hip (60% risedronate; 51% alendronate; not significant raloxifene) and vertebrae (49% risedronate; 47% alendronate; 30% raloxifene). A 5% discount rate was applied to cost and outcomes. In the base case, treatment with risedronate reduces costs from the social insurance perspective with respect to both endpoints: i.e., costs per averted hip fracture and QALY. Over the 3-year treatment period and 10-year observation, furthermore, risedronate proved superior to alendronate and raloxifene (i.e., risedronate was less expensive and more effective). From the perspective of statutory health insurance, the cost per averted hip fracture is 37,348 euro for risedronate and 48,349 euro for alendronate (costs for raloxifene were not calculated due to a nonsignificant effect on prevention of hip fractures); and cost per QALY gained is 32,092 euro for risedronate, in comparison to patients in Germany with no therapy (alendronate 41,302 euro; raloxifene 1,247,119 euro). This cost-effectiveness analysis gives evidence that bisphosphonates are cost effective. Under consideration of current prices and the published clinical evidence, risedronate dominates the comparison of DVO-recommended drugs.     

Fracture risk prediction with FRAX in Slovak postmenopausal women

Introduction

Current Slovak treatment thresholds in osteoporosis are based on bone mineral density (BMD) or a previous fracture. Some patients at high risk for fractures may not be identified. FRAX (Fracture Risk Assessment Tool) is based on patient risk profile assessment and calculates 10-year fracture risks. Using FRAX, treatment initiation could be more patient-specific.

Aim of study

To evaluate the risk profile with FRAX in slovak postmenopausal women, to identify those at high risk of fracture according to NOF (National Osteporosis Foundation) intervention thresholds based on FRAX and to compare this approach to current treatment thresholds.

Methods

We measured BMD at lumbar spine, femoral neck, total hip and calculated 10-year absolute fracture risks with the slovak version of FRAX in 365 patients.

Results

Average risk of major osteoporotic fracture was 10,39% and hip fracture 3,00%. 109 patients were eligible for treatment according to actual treatment criteria (88 based on BMD and 21 with previous fracture). In addition, 57 high risk osteopenic patients were identified by NOF thresholds using FRAX, who should be also considered for treatment.

Conclusion

Using FRAX and NOF thresholds it’s possible to identify high risk patients who don’t fulfill current treatment criteria but may profit from treatment.     

Oral nitrogen-containing bisphosphonates: a systematic review of randomized clinical trials and vertebral fractures

ABSTRACT

Background: Vertebral fractures are the most common osteoporotic fracture. They are associated with increased morbidity and mortality, and also predict future vertebral and non-vertebral fracture risk. Bisphosphonates are the current mainstay for the treatment of postmenopausal osteoporosis. Health authority guidelines request that assessment of vertebral fracture risk reduction is part of the evaluation of bisphosphonate efficacy. In this review, we compare the published evidence for the efficacy of the nitrogen-containing oral bisphosphonates in reducing the risk of vertebral fractures.

Methods: A review of publications in the treatment of postmenopausal osteoporosis and the most frequently prescribed oral bisphosphonate therapies (alendronate, ibandronate and risedronate) was carried out using the Dialog (Embase and Medline) and Cochrane online scientific citation databases. Eligible publications were those reporting randomized, placebo-controlled trials that included vertebral fracture as the primary or secondary endpoint (any time-point).

Results: Of 159 publications identified, six studies assessing alendronate, ibandronate and risedronate met the pre-defined eligibility criteria. In total, 14?083 women were included in the studies, with 8182 patients receiving active treatment. Most studies were 3?years in duration. Discontinuation rates varied from 11 to 45%, being highest in those studies that specified one or more vertebral fracture as part of the inclusion criteria. Across these studies, the reduction in the risk of vertebral fractures ranged from 41 to 62% (44–48% for alendronate; 41–49% for risedronate; 62% for ibandronate).

Conclusions: Nitrogen-containing oral bisphosphonates effectively reduce the risk of osteoporotic vertebral fracture, with the magnitude of effect ranging from 41 to 62%.     

强骨胶囊联合骨瓜提取物注射液治疗骨质疏松性股骨骨折的临床研究

目的探讨强骨胶囊联合骨瓜提取物注射液治疗骨质疏松性股骨骨折的临床效果。方法选取2015年6月—2017年6月上海市浦东新区光明中医院收治的98例骨质疏松性股骨骨折患者,随机分为对照组和治疗组,每组各49例。对照组静脉滴注骨瓜提取物注射液,100 mg加入250 m L生理盐水均匀混合,1次/d,连续治疗20 d为1个疗程,停药10 d;再按以上方案连用3个疗程。治疗组在对照组治疗基础上口服强骨胶囊,1粒/次,3次/d。两组均连续治疗3个月。观察两组的临床疗效,比较两组治疗1、3个月时骨痂骨密度(BMD)水平和骨愈合时间。比较两组治疗前后VAS评分、股骨颈BMD、HHS评分、钙(Ca)、磷(P)、碱性磷酸酶(ALP)、骨钙素(BGP)、24 h尿标本中羟脯氨酸(HOP)水平的变化情况。结果治疗后,对照组和治疗组的总有效率分别为79.59%、93.88%,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组治疗1、3个月时骨痂BMD值显著高于对照组治疗同期,治疗组骨折愈合时间显著短于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组VAS评分、Ca、ALP水平和24 h尿HOP显著降低,股骨颈BMD、HHS评分、P、BGP显著升高,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组VAS评分、Ca、ALP水平和24 h尿HOP低于对照组,股骨颈BMD、HHS评分、P、BGP显著高于对照组,两组比较差异具有统计学意义(P0.05)。结论强骨胶囊联合骨瓜提取物注射液治疗骨质疏松性股骨骨折具有较好的临床疗效,可有效减轻患者疼痛,增加骨密度,促进骨折愈合,调控骨代谢平衡,具有一定的临床推广应用价值。     

Relationship between bone mass,invasive breast cancer incidence and raloxifene therapy in postmenopausal women with low bone mass or osteoporosis

ABSTRACT

Objective: To evaluate the relationship between bone mass and risk of breast cancer and to determine the effect of raloxifene therapy on breast cancer incidence in women categorized by bone mass into low bone mass and osteo­porosis subgroups.

Design: In this post hoc analysis, data were analyzed from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, enrolling postmenopausal women with low bone mass (N = 7705), and the Continuing Outcomes Relevant to Evista (CORE) trial, a follow-up to MORE enrolling 4011 MORE participants. Total follow-up was for up to 8 years. Women with a total hip bone mineral density (BMD) T-score <?–1 to >?–2.5 or T-score ≤?–2.5 (referent, NHANES III database) were classified as having low bone mass or osteoporosis, respectively. Women with a pre-existing vertebral fracture were considered as having osteoporosis irrespective of BMD T-score. Analyses were performed for invasive breast cancers and invasive estrogen-receptor (ER) positive breast cancers.

Results: Women with low bone mass (N = 3829) had a twofold higher incidence of invasive ER-positive breast cancer than those with osteoporosis (N = 3836) (HR 2.13, 95% CI 1.12–4.03). The incidence of all invasive breast cancers did not differ significantly between the bone mass groups. The incidences of invasive and invasive ER-positive breast cancers were 65–78% lower in women assigned raloxifene versus placebo in both the low bone mass and osteoporosis groups (?p < 0.05).

Conclusions: In this post hoc analysis of postmeno­pausal women participating in MORE and CORE, bone mass was a predictor of invasive ER-positive breast cancer. Raloxifene treatment reduced the risk of invasive and invasive ER-positive breast cancers in women with low bone mass and those with osteoporosis. Since participants were older postmenopausal women with low bone mass, whether these findings can be generalized to other postmenopausal women is unclear.     

Modulatory effect of farnesyl pyrophosphate synthase (FDPS) rs2297480 polymorphism on the response to long-term amino-bisphosphonate treatment in postmenopausal osteoporosis

ABSTRACT

Introduction: Polymorphisms of genes encoding enzymes of the mevalonate pathway could modulate the response to amino-bisphosphonate treatment in postmenopausal osteoporosis.

Research design and methods: A characterisation of 234 Danish osteoporotic postmenopausal women (as part of the Prospective Epidemiological Risk Factors study (PERF)), treated for at least 2 years with amino-bisphosphonates, with respect to the adenosine/cytosine (A/C) rs2297480 farnesyl pyrophosphate synthase (FDPS) gene polymorphism, was carried out by PCR-based enzymatic digestion and quantitative PCR allelic discrimination on genomic DNA extracted from blood leukocytes. The association between these polymorphism genotypes and the response of spine and femur bone mineral density (BMD) and of biochemical bone biomarkers to treatment with amino-bisphosphonates was statistically examined.

Results: FDPS polymorphism did not show any relationship to baseline spinal and femoral BMD in Danish postmenopausal women. BMD response to treatment with amino-bisphosphonates was similar in the AA and the AC genotypes, while the CC genotype showed a lower BMD response to 2-year-treatment with amino-bisphosphonates at all examined skeletal sites (?p?=?0.60 at the spine and p?=?0.59 at the femur). Interestingly, after 2 years of treatment the response of urinary Cross-laps to amino-bisphosphonates treatment was significantly (?p?<?0.05) lower in the CC genotype when compared to both the AC and AA genotypes. Even the response of serum osteocalcin was lower in the CC genotype, but without reaching a statistical significance (?p?=?0.65).

Conclusions: Danish postmenopausal women with osteoporosis bearing the homozygous CC genotype for rs2297480 FDPS polymorphism showed a decreased response of bone turnover markers to amino-bisphosphonate therapy, when compared to the heterozygous AC and to the homozygous AA genotypes. Further investigation on larger and different populations, together with polymorphism functional studies are required to confirm these data.     

Treatment with alendronate plus calcium,alendronate alone,or calcium alone for postmenopausal low bone mineral density

ABSTRACT

Objective: Bisphosphonates such as alendronate are widely used for postmenopausal osteoporosis. Supplemental calcium is also generally recommended. This trial directly compares alendronate to supplemental calcium and examines the effect of calcium supplementa­tion on alendronate treatment.

Methods: This 2-year, randomized, double-blind, multicenter trial enrolled healthy, postmenopausal women with low bone mineral density (BMD). Patients with a dietary calcium intake ≥?800?mg/day received daily vitamin D 400?IU and alendronate 10?mg/calcium-placebo, alendronate 10?mg/elemental calcium 1000?mg, or alendronate-placebo/calcium 1000?mg (2:2:1). Endpoints included BMD, bone turnover markers (BTMs), and adverse events.

Results: Randomized patients (N = 701) were an average of 20.4 years postmenopausal. After 24 months, increases in lumbar spine BMD differed significantly between patients receiving calcium alone (0.8%) and either alendronate alone (5.6%) or alendronate + calcium (6.0%) (?p < 0.001). Significant differences were also seen at the trochanter and femoral neck (?p < 0.001). BTMs were significantly lower with alendronate-containing treatments than calcium alone (?p < 0.001). Addition of calcium supplementation to alendronate did not signif­icantly increase BMD compared to alendronate alone (?p = 0.29 to 0.97), but did result in a statistically significant, though small, additional reduction in urinary NTx. Adverse events were similar among treatment groups. Limitations include no assessment of vitamin D levels and a discontinuation rate of approximately 30%, although discontinuation rates were similar among treatment groups.

Conclusions: In postmenopausal women with a daily intake of ≥?800?mg calcium and 400?IU vitamin D, 24-month treatment with alendronate 10?mg daily with or without calcium 1000?mg resulted in significantly greater increases in BMD and reduction of bone turnover than supplemental calcium alone. Addition of supplemental calcium to alendronate treatment had no effect on BMD and resulted in a small, though statistically significant, additional reduction in NTx.     

Efficacy and safety of alendronate and risedronate for postmenopausal osteoporosis

ABSTRACT

Introduction: This paper discusses the efficacy and safety of alendronate and risedronate in the treatment of postmenopausal osteoporosis.

Methods: The literature was searched with the PubMed from 1996 to the present, with respect to strictly conducted systematic reviews with homogeneity, meta-analyses with homogeneity, and randomized controlled trials (RCTs) with narrow Confidence Interval.

Results: According to the results of large randomized controlled trials (RCTs), bisphosphonates (alendronate, risedronate, and ibandronate), raloxifene, calcitonin, parathyroid hormone (PTH), and strontium ranelate effectively prevent vertebral fractures in postmenopausal women with osteoporosis. Because raloxifene has been shown to be effective in preventing the initial vertebral fracture in postmenopausal osteoporotic women without prevalent vertebral fractures, it is considered in the treatment of postmenopausal women with mild osteoporosis or osteopenia with some risk factors for fractures. RCTs have also demonstrated that alendronate, risedronate, PTH, and strontium are useful to prevent non-vertebral fractures and that alendronate and risedronate prevent hip fractures, thus alendronate or risedronate are primarily considered as the first-line drugs in the treatment of elderly women with osteoporosis having some risk factors for falls. While it has been suggested that PTH may be considered in patients with severe osteoporosis, the use of PTH in the treatment for osteoporosis is limited to 2 years or less, and it may be appropriate to use other anti-resorptive drugs after the completion of PTH treatment to maintain the skeletal effects gained during the treatment. RCTs have demonstrated that the incidence of gastrointestinal tract adverse events in postmenopausal osteoporotic women treated with bisphosphonates and placebo are similar, and also the long-term efficacy and safety of alendronate and risedronate.

Conclusion: The evidence derived from the literature, based on strict evidence-based medicine guidelines, suggests that there is long-term efficacy and safety with alendronate and risedronate in the treatment of osteoporosis in postmenopausal women.     

Changes of bone mineral density in pre-menopausal women with differentiated thyroid cancer receiving L‐thyroxine suppressive therapy

ABSTRACT

Objective: We studied the effect of levothyroxine (L-T4) suppressive therapy on bone mineral density (BMD) in pre-menopausal women with total thyroidectomy and radioactive iodine (131I) ablation therapy post-operatively for differentiated thyroid cancer (DTC).

Patients and methods: We prospectively studied 26 athyroid pre-menopausal women (median age 39 years, range 28–48 years) receiving suppressive L‐T₄ therapy postoperatively for 48 months. BMD was measured by dual energy X‐ray absorptiometry (DEXA) at the femoral neck, femoral trochanter and Ward's triangle, before (basal) and during (12th and 48th month) the follow-up period. None of the women gave a medical history that could possibly affect bone metabolism. Patients were free of thyroid cancer in clinical and laboratory examinations at the time of the study. Paired t‐test was used for comparisons among BMD measurements during the suppressive therapy.

Results: There were statistically significant decreases of BMD at all measured regions during (12th and 48th month) L‐T₄ suppressive therapy. The overall decreases in BMD at the femoral neck, femoral trochanter and Ward's triangle were 7.5%, 10.9% and 3.4%, respectively, at the end of the follow-up period. The coefficient of variation (CV) of all BMD measurements was around 10%, showing a rather homogenous group of patients. Our patients had a statistically significant decrease in their body mass index (BMI) and weight at the end of the follow-up period. However, there was no significant correlation between the decrease in BMI and BMD. Patients did not experience significant adverse effects from L‐T₄ suppressive therapy during the study.

Conclusion: L‐T₄ suppressive therapy for at least 1 year in pre-menopausal women with DTC causes a reduction in BMD of the femoral neck, femoral trochanter and Ward's triangle.     

Effects of Alendronate and Calcitonin on Bone Mineral Density in Postmenopausal Osteoporotic Women. An Observational Study

Objective: Alendronate and calcitonin are antiresorptive drugs that were used for the treatment of postmenopausal osteoporosis and were shown to increase bone mineral density (BMD). However, the effect of both drugs in daily clinical practice may differ from that observed in clinical trials.Method: About 50 postmenopausal osteoporotic women were observed during their first year of treatment. Among them, 32 patients used alendronate and 18 used calcitonin. Lumbar spine and femoral neck BMD were measured by dual energy X-ray absorptiometry (DXA) at baseline and after 1 year of therapy. Biochemical markers (B-ALP – bone-specific alkaline phosphatase, OTC – osteocalcin and DPD/UCr – deoxypyridinoline/creatinine ratio) of bone metabolism were measured at baseline and 6 months later. Patient compliance was assumed by tablet counting and verified at interview. Each patient was further questioned about her attitude towards the treatment, as well as her dairy product intake, physical activity, use of other medications, smoking and social status.Main outcome measure: (1) Annual percent change in BMD in lumbar spine and femoral neck after the one-year treatment with either alendronate or calcitonin. (2) The change in biochemical markers of bone turnover.Results: The lumbar spine BMD significantly increased by 7.0% (P < 0.001), the femoral neck BMD by 4.3% (P < 0.01). OTC, B-ALP and DPD/UCr decreased significantly during the therapy with alendronate. Compliance with therapy was 79% (95% CI 68–90%). In the calcitonin-treated group, the lumbar spine BMD significantly increased by 3.1 % (P < 0.05), while the femoral neck BMD remained unchanged. OTC, B-ALP and DPD/UCr did not change significantly during the treatment with calcitonin. Compliance with calcitonin therapy was 87% (95% CI 63–110%). The annual change of BMD in both treatment groups was independent on all questioned factors.Conclusion: In daily practice, alendronate enhanced significantly BMD both in lumbar spine and femoral neck. Calcitonin showed increase only in the lumbar spine BMD.     

Potential role of FRAX analysis in postmenopausal women with osteopenia

Early diagnosis of osteoporosis and estimation of subjects that are at high risk for fracture, is neccesary for osteoporosis treatment. Dual-energy X-ray absorptometry (DXA) is a modern method for bone mineral density (BMD) evaluation. However, along BMD, clinical risk factors may significantly influence fracture development. Therefore, FRAX algorithm was designed for the assessment of a ten-year risk for serious osteoporotic fractures (SOF), as well as hip fractures. In the current study, we tried to evaluate the possible lumbal spine and hip BMD influence on ten year risk for SOF and hip fractures and potential role of FRAX in predicting the therapy in postmenopausal women with osteopenia. We performed the study on 385 postmenopausal women. According to the DXA measurements, at the lumbal (L) spine (L1–L4) and hip (femor neck), patients were then classified as normal, osteopenic, or osteoporotic. BMD evaluation included the L spine and the hip (subgroup 1), and only on the L spine (subgroup 2). By filling up the FRAX questionnaire, a ten-year risk for SOF fracture and hip fracture was calculated. BMD evaluation, in complete patient’s group and in subgroup 1, resulted in the highest number of osteoporosis (61.04%, 48.08%, retrospectively), while ospeopenia was a main finding in subgroup 2. In the subgroup 1, a high risk for SOF and hip fracture was detected in 16.45% and with high risk for hip fracture in 11.38% subjects. In subgroup 2, only high risk for hip fracture was observed in 3.16% subjects, indicating the active medicament treatment. Simultaneously, correlation of BMD results with FRAX values for SOF and hip fracture, showed significant negative correlation (p<0.001). Obtained results showed significant role of femur neck BMD evaluation in predicting the future factors, which may, together with FRAX analysis, improve the therapy approach in postmenopausal women with ospeopenia.     

Characterization of patients in the European Forsteo Observational Study (EFOS): postmenopausal women entering teriparatide treatment in a community setting

ABSTRACT

Objective: The European Forsteo^* Observational Study (EFOS) study was primarily designed to assess fracture incidence, degree of pain, health-related quality of life (HRQoL) and compliance in women prescribed teriparatide in a community setting. This report describes the design of the study and characteristics of the patients at entry.

Methods: At entry, 1645 postmenopausal women with a diagnosis of osteoporosis and about to initiate teriparatide treatment were enrolled in eight European countries. Baseline data were collected on demographic characteristics, medical and osteoporosis history, disease status, prior use of medications and HRQoL.

Results: The mean (standard deviation [SD]) age of patients was 71.5 (8.4) years, lumbar spine bone mineral density (BMD) T?score was –3.3 (1.2), the mean number of previous fractures reported after 40 years of age was 2.9 (2.0), 70% had two or more vertebral deformities and 91.7% were pre-treated with bisphosphonates. HRQoL, evaluated by the health state value (HSV) (median: 0.59, Q1; Q3: 0.08; 0.71) and visual analogue scale (VAS) (median 50.0, Q1; Q3: 35.0; 69.0) status of the European quality of life questionnaire (EQ?5D) was poor. Extreme problems were reported by 31% of patients for the pain/discomfort dimension, mobility was limited in 69% and anxiety/depression was reported by 57% of patients. Chronic or intermittent back pain was reported by 91% of patients, which occurred every day or almost every day within the last month in 66% of patients.

Conclusions: The post-menopausal women prescribed teriparatide were severely osteoporotic, with a high fracture risk and poor HRQoL, despite previous therapy for osteoporosis. Moderate to severe back pain was very common.     

The effect of raloxifene therapy on the risk of new clinical vertebral fractures at three and six months: a secondary analysis of the MORE trial

ABSTRACT

Objective: Raloxifene treatment (60?mg/day) significantly decreases the risk of new clinical vertebral fractures by 68% at 1 year compared with placebo. The objective of the present analysis is to evaluate the effects of raloxifene on the incidence of new clinical vertebral fractures at 3 and 6 months after initiation of treatment.

Research design and methods: A double-blind, randomized, placebo-controlled, 4‐year Multiple Outcomes of Raloxifene Evaluation (MORE) trial was conducted in 180 study centers. Postmenopausal women with osteoporosis (N = 7705) were randomized to placebo, or raloxifene at 60 or 120?mg/day.

Main outcome measures: Vertebral radiographs were obtained when patients reported symptoms suggestive of vertebral fracture at or between clinic visits, which were held at 3 and 6 months, and every 6 months thereafter. If a new adjudicated fracture was found, this was considered as a clinical vertebral fracture. The analyses included all randomized patients with a baseline and at least one follow-up radiograph (n = 6828).

Results: One woman treated with raloxifene 60?mg/day (n = 2259) and 10 in the placebo group (n = 2292) had a clinical vertebral fracture in the first 6 months, resulting in a 90% relative risk (RR) reduction [RR 0.10 (95% CI 0.01, 0.63)] and a 0.39% absolute risk reduction (ARR). Similar results were observed with raloxifene 120?mg/day at 6 months. When the raloxifene groups were pooled, a significant (?p = 0.034) decrease in clinical vertebral fracture risk [RR 0.20 (95% CI 0.03, 0.90), ARR 0.17%] was seen as early as 3 months.

Conclusion: The risk of new clinical vertebral fractures was reduced after 3 or 6 months of raloxifene.     

Ibandronate produces significant,similar antifracture efficacy in North American and European women: new clinical findings from BONE

ABSTRACT

Objectives: BONE (oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe) determined whether less frequent dosing of ibandronate (dose-free interval > 2?months) provided similar antifracture efficacy to daily dosing. As osteoporosis medications must be effective across different populations, an additional objective of BONE was to investigate and report the effect of oral ibandronate in North American and European women, as described here.

Patients and methods: BONE was a randomized, double-blind, placebo-controlled, fracture-prevention study in 2946 postmenopausal women (age 55?years?80?years; ≥ 5?years since menopause) with osteoporosis (low lumbar spine bone mineral density and one to four prevalent vertebral fractures [T4?L4]). Participants received daily calcium (500?mg) and vitamin D (400?IU) plus either placebo, oral daily ibandronate (2.5?mg) or oral intermittent ibandronate (20?mg every other day for 12 doses every 3?months). The efficacy and tolerability of ibandronate were assessed independently in both North American and European populations.

Results: Consistent, significant efficacy was observed in the North American (new vertebral fracture risk reduction: 60% and 54% with daily and intermittent ibandronate, respectively) and European patient populations (50% and 48%, respectively). Both ibandronate regimens also significantly reduced the incidence of new, worsening, and acute clinical, vertebral fractures. Daily and intermittent ibandronate significantly increased bone density at the spine in both North American (5.4% and 4.4% vs. baseline with daily and intermittent ibandronate, respectively) and European (7.1% and 6.3% vs. baseline, respectively) populations. Significant increases were also observed for total hip bone density (2.6% and 3.7% vs. baseline for daily, and 2.5% and 3.1% for intermittent; North American and European populations, respectively). Comparable, significant decreases in biochemical markers of bone turnover (reductions in urinary excretion of C-telopeptide levels of 53.5% and 67.1% vs. baseline for daily, and 50.0% and 53.8% for intermittent; North American and European populations, respectively) were also observed in both populations (?p < 0.004 for all cited measurements in each ibandronate group vs. placebo). Oral ibandronate was well tolerated in both North American and European patients, with a safety profile similar to placebo.

Conclusions: Oral ibandronate, administered daily or intermittently, effectively reduced vertebral fracture risk in North American and European women with postmenopausal osteoporosis. These results demonstrate the efficacy of ibandronate administered with extended dose-free intervals, regardless of patients’ geographical origin. Research investigating other less frequent ibandronate regimens, such as once-monthly oral administration, is underway.     

雷奈酸锶治疗骨质疏松症的疗效及安全性的Meta分析

目的系统评价雷奈酸锶治疗骨质疏松症的疗效及安全性。方法检索Cochrane的RCT中心数据库、Embase、PubMed、CNKI数据库和维普数据库中雷奈酸锶治疗骨质疏松症的临床研究,按照纳入及排除标准筛选出随机对照试验,使用"Cochrane协作网的偏倚评论指标"评估搜集的文献质量。提取有效数据,采用RevMan 5.3软件进行Meta分析。结果共纳入双盲、随机对照试验6项,结果表明,雷奈酸锶治疗12个月后,腰椎、髋部及股骨颈骨密度提升度比安慰剂对照组分别高6.72%(95%CI:6.17%~7.27%,P<0.01)、3.97%(95%CI:3.53%~4.40%,P<0.01)及3.51%(95%CI:3.21%~3.81%,P<0.01)。雷奈酸锶组的不良反应发生率、因不良反应导致的患者退出率和安慰剂组相似,差异无统计学意义(P>0.05);雷奈酸锶组的皮肤和胃肠道不良反应事件发生率高于安慰剂组,差异有统计学意义(P<0.05)。结论相对于安慰剂对照,雷奈酸锶可显著提高腰椎、髋部及股骨颈骨密度,两者的安全性近似。