Risedronate Group Research Articles

Comparative effects of risedronate, atorvastatin, estrogen and SERMs on bone mass and strength in ovariectomized rats

Objective The aim of this study was to investigate bone protective effects of risedronate, atorvastatin, raloxifene and clomiphene citrate in ovariectomized rats. Methods Our study was conducted on 63 rats at Experimental Research Center of Celal Bayar University. Six-month-old rats were divided into seven groups. There were five drug administered ovariectomized groups, one ovariectomized control group without drug administration and one non-ovariectomized control group without drug administration. Eight weeks postovariectomy, rats were treated with the bisphosphonate risedronate sodium, the statin atorvastatin, the estrogen 17β-estradiol and the selective estrogen receptor modulators (SERMs) raloxifene hydrochloride and clomiphene citrate by gavage daily for 8 weeks. At the end of the study, rats were killed under anesthesia. For densitometric evaluation, left femurs and tibiae were removed. Left femurs were also used to measure bone volume. Right femurs were used for three-point bending test. Results Compared to ovariectomized group, femur cortex volume increased significantly in non-ovariectomized group ( p = 0.016). Compared to non-ovariectomized group, distal femoral metaphyseal and femur midshaft bone mineral density values were significantly lower in ovariectomized group ( p = 0.047). In ovariectomy + atorvastatin group, whole femur and femur midshaft bone mineral density and three-point bending test maximal load values were significantly higher than ovariectomized group ( p = 0.049, 0.05, and 0.018). When compared to the ovariectomized group, no significant difference was found with respect to femoral maximum load values in groups treated with risedronate, estrogen, raloxifene and clomiphene ( p = 0.602, 0.602, 0.75, and 0.927). In ovariectomy + risedronate group, femur midshaft bone mineral density values were significantly higher than the values in ovariectomized group ( p = 0.023). When compared to ovariectomized group, no significant difference was found with respect to femur midshaft bone mineral density values in groups treated with estrogen, raloxifene and clomiphene ( p = 0.306, 0.808, and 0.095). Conclusions While risedronate sodium prevented the decrease in bone mineral density in ovariectomized rats, atorvastatin maintained mechanical characteristics of bone and also prevented the decrease in bone mineral density as risedronate sodium.

Risedronate Recovers Bone Loss in Patients With Prostate Cancer Undergoing Androgen-deprivation Therapy

To perform a prospective observational study between risedronate and no risedronate (control) groups to determine the effectiveness of risedronate against bone loss in patients with prostate cancer (PCa) receiving androgen-deprivation therapy (ADT). ADT for PCa has iatrogenic complications (eg, bone loss and fracture). We enrolled 60 Japanese patients with PCa who were receiving ADT or were newly scheduled for ADT. The lumbar spine bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry. Patients with a BMD <90% of the young adult mean received risedronate. We analyzed 29 and 27 patients in the risedronate and control groups, respectively. The BMD, urinary deoxypyridinoline, and serum bone alkaline phosphatase were measured as bone turnover markers at 6 and 12 months. The BMD/young adult mean ratio correlated inversely with the duration of ADT. The initial mean BMD was significantly lower in the risedronate group than in the control group (1.02 +/- 0.19 vs 1.19 +/- 0.16 g/cm(2)). We focused on patients treated with ADT for >6 months. The mean percentage of changes in the BMD/young adult mean ratio of the risedronate and control groups was +2.6 +/- 4.5% and -2.8 +/- 2.6% after 1 year, respectively (P = .0001). The urinary deoxypyridinoline and bone alkaline phosphatase in the risedronate group decreased significantly after 12 months compared with the levels in the controls. The results of our study have shown that oral administration of risedronate is effective for the recovery of ADT-induced bone loss in patients with PCa.

Once-Weekly Risedronate in Men With Osteoporosis: Results of a 2-Year, Placebo-Controlled, Double-Blind, Multicenter Study

Male osteoporosis is increasingly recognized as a major public health issue. This multinational, 2-yr, randomized, double-blind, placebo-controlled study was conducted to determine the efficacy and safety of 35 mg once-a-week risedronate in men with osteoporosis. Patients had to be men >or=30 yr old, with lumbar spine T-score <or= -2.5 and femoral neck T-score <or= -1 SD or lumbar spine T-score <or= -1 and femoral neck T-score <or= -2 SD (based on young normal men). Patients were randomized 2:1 to risedronate 35 mg once a week or placebo for 2 yr; all patients took 1000 mg elemental calcium and 400-500 IU vitamin D daily. Lumbar spine BMD at month 24 using last observation carried forward was the primary endpoint. Other endpoints included lumbar spine BMD at time points other than month 24, proximal femur BMD, bone turnover markers (BTMs), new vertebral fractures, clinical fractures, and adverse event (AE) assessment. There were 284 men enrolled in the study. Treatment with risedronate resulted in a significant increase from baseline to endpoint in lumbar spine BMD compared with placebo (4.5%; 95% CI: 3.5%, 5.6%; p < 0.001). Few new vertebral and nonvertebral fractures were reported, with no differences in fracture rates between the two groups. There was a significant (p < 0.01) reduction from baseline in BTMs for the risedronate group compared with placebo at all time points. No apparent differences in the pattern or distribution of AEs including serious and upper gastrointestinal AEs were observed. Risedronate therapy was well tolerated during this 2-yr study and was rapidly effective as indicated by significant BTM decreases at month 3 and BMD increases at month 6 (the earliest time points tested). The effects of risedronate treatment on BMD and BTMs in this study were similar to those previously shown to be associated with fracture risk reductions in women with postmenopausal osteoporosis.

Skeletal dysplasia and lethality in mice lacking the mid-region, nuclear localization signal and C-terminus of parathyroid hormone-related protein

Introduction: Age-related bone loss is associated with high levels of adipogenesis within the bone marrow. Since osteoblasts and adipocytes share a common marrow stromal cell precursor, it is possible that with aging, there is a preferential “switch” in commitment of this precursor to the adipocyte over the osteoblast lineage. Previously, we have reported a potential anabolic effect of bisphosphonates through the stimulation of osteoblastogenesis and inhibition of adipogenesis in vitro (Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells. Duque G, Rivas D. J Bone Miner Res. 2007, 22:1603–11). In the current study, we tested the hypothesis that the effect of bisphosphonates on marrow adipogenesis in vitro is also present in vivo. Methods: We analyzed transiliac bone biopsies from a randomized, placebo-controlled clinical trial that evaluated the effects of risedronate treatment 5 mg/day on vertebral and non-vertebral fractures in women with postmenopausal osteoporosis. Paired bone biopsies were obtained from a subset of patients at baseline and after treatment with placebo or risedronate for 3 years (placebo, n=18, risedronate, n=14). Biopsies were stained with toluidine blue and hematoxylin/eosin. Adipocyte volume/tissue volume (AV/TV) adipocyte number (Ad#) and mean adipocyte size were quantified. Results: In the placebo group AV/TV and Ad# significantly increased (<15%). In contrast, there were significant decreases in these parameters (<28%) in the risedronate group (p<0.01). In addition, mean adipocyte size was significantly reduced (<25%) in the risedronate group (p<0.01) at 3 years. Conclusion: Risedronate reduces marrow adipogenesis in postmenopausal women, independently of its effect on bone mass. These findings are the first demonstration of an effect of bisphosphonates on marrow fat in humans in vivo. This effect may contribute to the beneficial effect of bisphosphonates on bone mass. (1) Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells. Duque G, Rivas D. J Bone Miner Res. 2007, 22:1603–11.

Bisphosphonates and Bone Turnover in Premenopausal Women Receiving Adjuvant Chemotherapy

Bisphosphonates and Bone Turnover in Premenopausal Women Receiving Adjuvant Chemotherapy

Marked reduction of bone turnover by alendronate attenuates the acute response of bone resorption marker to endogenous parathyroid hormone

The aim of this study was to assess the effects of the antiresorptive treatments of alendronate (ALN), risedronate (RIS) and raloxifene (RLX) on the response of bone to endogenous parathyroid hormone (PTH) induced by acute hypocalcemia. Forty women (age, 55–80 years) with postmenopausal osteoporosis (treated with ALN, RIS and RLX or untreated-control group) were given infusions of sodium ethylenediaminetetraacetic acid (EDTA; 10 mg/kg of body weight). Serum ionized calcium (iCa), plasma intact PTH and marker of bone resorption, serum β C-terminal telopeptide of type I collagen (β-CTX; β CrossLaps) were followed for 180 min. In all women, decrease in serum iCa following the EDTA load resulted in an acute increase in serum PTH. Between 60 and 180 min, plasma PTH in the ALN and RIS treated women remained significantly higher than in the control group. The integrated β-CTX responses (area under curves, AUCs) to peaks of PTH were significantly lower in the ALN treated women than in those treated with RIS, RLX or control group. There was no significant difference in β-CTX AUC response to PTH between RIS, RLX and control women. Taken together, these findings suggest that in women with postmenopausal osteoporosis treated with ALN, a substantial reduction of bone turnover blunts the acute bone resorbing effect of endogenous PTH.

Early Responsiveness of Women with Osteoporosis to Teriparatide After Therapy with Alendronate or Risedronate

Anabolic responsiveness to teriparatide can be blunted or delayed in patients previously treated with alendronate. The extent of this effect is different for other antiresorptives. This study evaluated the early anabolic effects of teriparatide in postmenopausal women with osteoporosis previously treated with alendronate or risedronate. Patients treated for at least 24 months with alendronate or risedronate discontinued their bisphosphonate and received teriparatide for 12 months. The primary endpoint was a comparison of changes from baseline in N-terminal propeptide of type 1 collagen after 3 months between prior bisphosphonate groups. We also examined changes in other bone turnover markers, bone mineral density (BMD), and relationships between early changes in bone turnover markers and 12-month areal and volumetric BMD. In the prior risedronate group, the N-terminal propeptide of type 1 collagen increase was significantly greater after 3 months of teriparatide than in the prior alendronate group (mean +/- se, 86.0 +/- 5.6 vs. 61.2 +/- 5.3 ng/ml, respectively; P < 0.001). Findings were similar for the other bone turnover markers. The changes in areal BMD and trabecular spine volumetric BMD were also greater in the prior risedronate group (P < 0.05). Early changes in bone turnover markers correlated with changes in trabecular spine volumetric BMD at 12 months (Spearman r = 0.45). Teriparatide was well tolerated. This nonrandomized but prospective study suggests that there may be differences in anabolic responsiveness to teriparatide as a function of the type of prior bisphosphonate exposure.

Effects of risedronate on metabolic bone disease in patients with type 1 diabetes and osteoporosis

To assess the effect of a antiresorptive on bone mass and remodeling markers in patients with type 1 diabetes mellitus (DM-1) and osteoporosis (OP). Study included 52 patients with DM-1 of 21-36 years duration and OP or osteopenia, aged 29-69 years. OP patients received 30 mg/week risedronate (n = 35) and calcium + vitamin D; osteopenic patients and risedronate refusers (n = 17) received only calcium + vitamin D. At 12 months, the risedronate group showed significant improvements in tartrate resistant acid phosphatase (p

Effectiveness of risedronate in osteoporotic postmenopausal women with inflammatory bowel disease

To evaluate long-term efficacy of risedronate in osteoporotic postmenopausal patients with inflammatory bowel disease (IBD). A prospective, parallel, open-label, 2-year extension study of a randomized, double-blind, 1-year clinical trial. Eighty-one osteoporotic postmenopausal women with IBD were treated with risedronate (n = 40) or placebo (n = 41). Bone mineral density (BMD), biochemical bone turnover markers, and vertebral and nonvertebral fractures were assessed throughout the study. Data were analyzed using the intent-to-treat principle. Significant (P < 0.05) differences were observed between risedronate and placebo groups at 1-, 2-, and 3-year follow-up visits in bone turnover markers and in lumbar spine, trochanter, and femoral neck BMD. In participants treated with risedronate, the percentage of changes from baseline in bone turnover markers and in lumbar spine, trochanter, and femoral neck BMD were significantly (P < 0.05) higher at 2- and 3-year follow-up in comparison with baseline and 1-year follow-up, with a significant (P < 0.05) difference between the 2- and 3-year follow-up visits. At the end of the study, the cumulative risk of vertebral and nonvertebral fractures was significantly (P < 0.05) lower in the risedronate group than in the placebo group. The relative risk for new vertebral fractures was 0.456 (95% CI: 0.134-1.559, P = 0.211) and 0.296 (95% CI: 0.121-0.721, P = 0.007) and was 0.209 (95% CI: 0.023-1.867, P = 0.161) and 0.137 (95% CI: 0.030-0.620, P = 0.010), respectively, for new nonvertebral fractures after 2 and 3 years of risedronate treatment. In postmenopausal osteoporotic women with IBD, long-term treatment with risedronate is effective in increasing BMD and reducing vertebral and nonvertebral fracture risk.

Risedronate Prevents Bone Loss in Breast Cancer Survivors: A 2-Year, Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Limited data are available on the efficacy of oral bisphosphonate therapy in breast cancer survivors. Our goal was to examine prevention of breast cancer-related bone loss in this cohort. Eighty-seven postmenopausal women after chemotherapy for breast cancer were randomly assigned to once-weekly risedronate 35 mg or placebo for 24 months. Outcomes included bone mineral density (BMD) and turnover markers. At study initiation, 13% of patients were on an aromatase inhibitor (AI). After 24 months, there were differences of 1.6 to 2.5% (P < .05) at the spine and hip BMD between the placebo and risedronate groups. At study completion, 44% were on an AI. Adjusting for an AI, women on placebo plus AI had a decrease in BMD of (mean +/- SE) 4.8% +/- 0.8% at the spine and 2.8% +/- 0.5% at the total hip (both P < .001). In women on risedronate + AI, the spine decreased by 2.4% +/- 1.1% (P < .05) and was stable at the hip. Women in the placebo group not on an AI, maintained BMD at the spine, and had a 1.2% +/- 0.5% loss at the total hip (P < .05). Women who received risedronate but no AI had the greatest improvement in BMD of 2.2% +/- 0.9% (P < .05) at the total hip. Bone turnover was reduced with risedronate. There were no differences in adverse events between the groups. We conclude that in postmenopausal women with breast cancer with or without AI therapy, once-weekly oral risedronate was beneficial for spine and hip BMD, reduced bone turnover, and was well tolerated.

Head-to-head comparison of risedronate vs. teriparatide on bone turnover markers in women with postmenopausal osteoporosis: a randomised trial

We aimed to compare the effect of risedronate (RIS) and teriparatide (TPTD) (recombinant human parathyroid hormone 1-34) on bone turnover markers in women with postmenopausal osteoporosis. Forty-four Caucasian women (age 65.1 +/- 1.6 years) with postmenopausal osteoporosis were randomly assigned to receive either RIS 35 mg once weekly (n = 22) or TPTD 20 microg once daily (n = 22) for 12 months. Serum N-terminal propeptide of type 1 collagen (P1NP), C-terminal telopeptide of type 1 collagen (CTx), total alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) were obtained from all women before, 3 and 6 months after treatment initiation. Lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry before and 12 months after treatment initiation. P1NP, CTx and total ALP levels decreased in RIS group (p < 0.001) and increased in TPTD group (p < 0.001) throughout the treatment. iPTH increased significantly in RIS group (p < 0.05) and decreased in TPTD group (p < 0.001). Finally, lumbar spine BMD increased significantly in both RIS (p = 0.003) and TPTD groups (p < 0.001) without significant differences between them. Our data suggest that both serum P1NP and CTx are reliable markers of RIS and TPTD action in women with postmenopausal osteoporosis. In a similar way, serum total ALP can be used as an alternative marker for monitoring both RIS and TPTD action, while iPTH can be used only for TPTD-treated women. The increase in P1NP and CTx after 3 months of treatment with RIS or TPTD can predict the increase in BMD after 12 months of treatment.

前立腺癌のアンドロゲン除去療法におけるビスフォスフォネートの臨床的意義

Androgen deprivation therapy (ADT) in patients with prostate cancer is associated with bone loss. We investigated the effectiveness of risedronate about a decreasing bone mineral density in patients with prostate cancer on ADT. A prospective study was conducted in Kitasato University Hospital from April 2004 to October 2006. A total of 69 men with prostate cancer were assigned to receive either oral risedronate or none during ADT (hormone naïve). The treatment group was 58 men and taking 2.5 mg risedronate per day. The control group was 11 men. At baseline, we assessed BMD (bone mineral density) by DEXA and urinary NTX, and measured for these changes every 6 months. At baseline, each BMDs had no significant difference at the lumber and total hip. At the first 6-month stage, the change in BMD percentage between the 2 groups was statistically significantly different at lumber (p = 0.002) and total hip (p = 0.038). At the 12-month stage, the change in the BMD percentage between the 2 groups was statistically significantly different at the lumber (p = 0.038). And each difference made out that the risedronate group was preserving BMD. In urinary NTX, bone turn over was statistically significantly decreased with the risedronate group compared with the control group at the 12-month stage (p = 0.017). We assure the beginning of bone loss at an early date (6 months) with ADT. Daily oral risedronate in patients with receiving ADT reduces bone mineral loss and maintain BMD.

Risedronate for prevention of bone mineral density loss in patients receiving high-dose glucocorticoids: a randomized double-blind placebo-controlled trial

This 6-month randomized double-blind placebo-controlled trial shows that risedronate is well tolerated and effective in improving lumbar spine BMD and reducing loss of BMD at the hips in patients receiving high-dose prednisolone. Bisphosphonates have proven benefits in patients receiving chronic low-dose glucocorticoids. However, whether they are effective in preventing bone mineral density (BMD) loss during periods of high-dose glucocorticoid treatment is unclear. The objective of this paper is to study the efficacy of risedronate in preventing bone mineral density (BMD) loss in users of high-dose glucocorticoids. Adult patients with medical diseases treated with high-dose prednisolone (>0.5 mg/kg/day) were randomized to receive risedronate (5 mg/day) or placebo for 6 months in a double-blind manner, along with elemental calcium (1,000 mg/day). Changes in BMD were studied. One hundred and twenty patients were recruited (82 women, age 42.8 +/- 14.3 years, 63% corticosteroid-naive, 30% women postmenopausal) and 103 completed the study. Baseline clinical characteristics and BMD were similar in the risedronate and placebo groups. At 6 months, a significant gain in spinal BMD was observed in the risedronate group (+0.7 +/- 0.3%; p = 0.03) but a drop was detected in the placebo group (-0.7 +/- 0.4%; p = 0.12). After adjustment for baseline BMD, age, gender, body mass index and cumulative prednisolone dosages, the inter-group difference in spinal BMD remained significant (1.4%; p = 0.006). Both groups had a significant drop in hip BMD, but the magnitude was greater in the placebo arm (-0.8 +/- 0.4% in risedronate versus -1.3 +/- 0.5% the in placebo). No new fractures developed. Subgroup analysis of corticosteroid-naive patients yielded similar results. Upper gastrointestinal adverse events were numerically more frequent in the risedronate group. Risedronate improves spinal BMD in users of high-dose glucocorticoids.

Fracture risk remains reduced one year after discontinuation of risedronate

One year after discontinuation of three year's treatment with risedronate, BMD decreased at the lumbar spine and femoral neck and bone turnover markers returned to control group levels. Despite these changes, the risk of new morphometric vertebral fractures remained lower in previous risedronate patients compared with previous control patients. Differences in bisphosphonate pharmacology and pharmacokinetics could influence persistence or resolution of the effects once treatment is stopped. We investigated changes in intermediate markers--bone mineral density (BMD) and bone turnover markers (BTM)--and fracture risk after discontinuation of treatment with risedronate. Patients who received risedronate 5 mg daily (N = 398) or placebo (N = 361) during the VERT-NA study stopped therapy per protocol after 3 years but continued taking vitamin D (if levels at study entry were low) and calcium and were reassessed one year later. In the year off treatment, spine BMD decreased significantly, but remained higher than baseline (p < or = 0.001) and placebo (p < 0.001), with similar findings at the femoral neck and trochanter. Urinary NTX and bone-specific alkaline phosphatase, which decreased significantly with treatment, were not significantly different from placebo after 1 year off treatment. Despite the changes in intermediate markers, the incidence of new morphometric vertebral fractures was 46% lower in the former risedronate group compared with the former placebo group (RR 0.54 [95% CI, 0.34, 0.86, p = 0.009]). Despite the apparent resolution of effect on BMD and BTM, the risk reduction of new vertebral fractures remained in the year after treatment with risedronate was stopped.

Effects of risedronate 5 mg/d on bone mineral density and bone turnover markers in late-postmenopausal women with osteopenia: A multinational, 24-month, randomized, double-blind, placebo-controlled, parallel-group, phase III trial

Background: Randomized clinical trials have shown that risedronate reduces the risk for both ver- tebral and nonvertebral fractures in postmenopausal women with osteoporosis (bone mineral density [BMD] T-score, <-2.5). If left untreated, osteopenia (T-score, between -1 and -2.5) may progress to osteo- porosis. Risedronate sodium, a pyridinyl bisphospho- nate, is an antiresorptive drug approved by the US Food and Drug Administration for the prevention and treatment of osteoporosis in postmenopausal women. Although the effects of risedronate in preventing frac- tures has been established, its effects in maintaining or increasing BMD in osteopenia have not. Objective: In this clinical trial, the efficacy and tol- erability of risedronate in improving and maintaining BMD levels in late-postmenopausal women with os- teopenia were assessed. Methods: This 24-month, randomized, double- blind, placebo-controlled, parallel-group, Phase III trial was conducted at 14 study centers across Finland, The Netherlands, Norway, Spain, and Sweden. Late- postmenopausal (≥5 years from menopause) women with lumbar spine (LS) BMD T-score between -1 and -2.5 and the presence of ≥1 additional risk factor for osteo- porosis or proximal femur (Fern) BMD T-score ≤-1 were randomized to receive risedronate 5 mg (n = 114) or placebo (n = 57) PO QD for 24 months. The primary efficacy end point was the percentage change from baseline in LS BMD at study end point (24 months or last observation carried forward). Secondary efficacy end points were the percentage changes from base- line in total proximal Fern BMD and 2 bone turnover markers—urinary type I collagen cross-linked N-telopeptide (uNTx) and serum bone-specific alkaline phosphatase (sBAP)—at 12 months and study end point. Tolerability was assessed using reported adverse events (AEs), laboratory analysis, and physical exami- nation including vital-sign measurements. Results: A total of 171 women were included (mean [SD] age, 65.9 [6.8] years; mean [SD] LS BMD T-score,-1.82 [0.42]; risedronate group, 114 patients; placebo group, 57). At study end point, LS BMD had significantly increased from baseline in the risedronate group ( P < 0.05) but remained unchanged in the placebo group (mean [SE] %Δ, +4.49% [0.38%] and +0.05% [0.54%], respectively; P < 0.001). Between- treatment differences in mean (SE) percentage changes from baseline in LS BMD and Fem BMD were signif- icant at 12 months and study end point (LS BMD, both P < 0.001; Fem BMD, P = 0.002 and P < 0.001, respectively). At 12 months and study end point, ris- edronate use was associated with significantly reduced concentrations of uNTx and sBAP compared with placebo (both, P < 0.001). Risedronate treatment was well tolerated with regard to gastrointestinal AEs; the most frequent AEs in the risedronate group were hy- pertension (n = 13), constipation (n = 8), and hyper- cholesterolemia (n = 8). Conclusions: In these late-postmenopausal women with LS osteopenia and ≥1 additional risk factor or hip osteopenia, 24-month treatment with risedronate 5 mg/d was associated with the prevention of bone loss at the spine and hip (based on significant increases in BMD in the LS and total proximal Fem) and reduced bone resorption (based on significantly reduced concen- trations of uNTx and sBAP) and was well tolerated.

Hip fractures in users of first- vs. second-generation bisphosphonates

This study compared population hip fracture rates for women with a prior fragility fracture who were treated with first-generation versus second-generation bisphosphonate therapies. The observational study found that, relative to women treated with etidronate, a first-generation bisphosphonate, women treated with the second-generation therapies 'alendronate' or 'risedronate' were equally likely to be admitted to hospital for hip fracture. Our findings must be confirmed in large randomized head-to-head controlled trials. Few studies have examined hip fracture outcomes among users of first- versus second-generation bisphosphonates. We compared hip fracture rates among elderly women with a history of fracture dispensed first- and second-generation bisphosphonates, hypothesizing that hip fracture rates would be higher among users of first- versus second-generation bisphosphonates after adjusting for confounders. Administrative data from Ontario, Canada from 01 April 1998 to 31 March 2002 was used to identify population-based bisphosphonate-naïve cohorts of subjects age 66 years and older initiated on first- (etidronate plus calcium; n = 19,127) or second-generation (alendronate or risedronate; n = 1,460) bisphosphonates. Multivariate Cox proportional hazard models were used for analysis. During over 23,000 person-years of follow-up, we observed 293 hospital admissions for first hip fracture. The unadjusted event rates yielded approximately 12.5 hospital admissions for hip fracture per 1,000 person-years of follow-up in each study group. Relative to the etidronate plus calcium group, females in the alendronate or risedronate group were equally likely to be admitted for hip fracture (adjusted rate ratio [aRR] = 1.0; 95% CI 0.6-1.6). The findings of this study suggest similar rates of hip fracture between the first- and second-generation bisphosphonates when used continuously among elderly females with a prior history of fracture.

Factors affecting long-term compliance of osteoporotic patients with bisphosphonate treatment and QOL assessment in actual practice: alendronate and risedronate

The aim of our study was to examine compliance with a daily dose of 5 mg alendronate (ALN) and 2.5 mg risedronate (RDN) in actual practice, and to determine the causes of noncompliance through a questionnaire. In addition, we studied the quality of life (QOL) of patients through another disease-related questionnaire. The overall compliance rate remained at approximately 40% one year after the initial dose. The rates did not differ significantly between the ALN group (783 patients) and the RDN group (491 patients). The compliances in the female group and the rheumatism group were better than in the male group and the nonrheumatism group. From the questionnaire, 36% of noncompliant patients showed adverse effects (AEs), and the other noncompliant patients stopped the medication in spite of having no AEs. A logistic regression analysis of factors that might have affected long-term compliance included AEs, an understanding of the disease, the method of ingestion, visiting medical facilities, the shape of the tablet, the cost of the drug, and the explanation of the doctor or pharmacist. This analysis showed that noncompliance occurred mainly due to AEs, the inconvenience of visiting a medical facility, unusual methods of ingestion, and a poor understanding of the disease. According to the results of the questionnaire for QOL assessment, the patients who continued the medication for more than 1 year had improved scores for pain in both the ALN and RDN groups. Osteoporotic treatment needs long-term patient compliance. To improve compliance, it is very important that doctors and pharmacists ensure that patients understand the purpose of this therapy.

Treatment of osteoporosis in men

Osteoporosis in men is recognised worldwide as an important and increasing public health problem. The causes are more heterogeneous than those in women. About 50% are diagnosed as secondary cases. In some secondary forms of osteoporosis the specific diagnosis results in additional therapeutic options (e.g. androgen therapy in proven hypogonadism). The basic therapy for osteoporosis in men is no different to that in postmenopausal women, namely recommendations for counteracting modifiable risk factors, especially with regard to diet, physical exercise, and calcium and vitamin D supplementation. Concerning specific drug medications, however, even today there is still a therapeutic dilemma in male osteoporosis. While older substances (e.g. calcitonin, fluoride, alfacalcidol) are approved for both sexes, all newer medications have primarily been approved for the treatment of postmenopausal osteoporosis. Health authorities request studies in purely male populations. For new drugs, fracture data are necessary while for new substances within a class (e.g. bisphosphonates), at the very least consistent effects on bone mineral density (BMD) and bone turnover markers are requested. Due to these regulatory rules, ibandronate, teriparatide and strontium ranelate are not approved in the European Union. Some years ago, alendronate was the first bisphosphonate that was approved for the treatment of men with osteoporosis, based on consistent results from two independent male studies using a daily 10 mg dosage. Very recently risedronate was approved by the FDA and EMEA. A randomised, placebo-controlled multicentre trial of 285 male patients showed, after 2 years, a 5.8% increase in lumbar spine BMD in the risedronate 35 mg once weekly group vs 1.2% in the placebo group. In a prospective controlled study on 316 men with primary or secondary osteoporosis we found, after 12 months, a lumbar spine BMD of +4.7% vs +1.0% in controls. The number of patients with one or more new vertebral fractures was 8 in the risedronate group and 20 in the placebo group (a fracture reduction of 60%). Furthermore, we found a significantly smaller decrease in height and a steeper decrease in back pain in the risedronate group. Risedronate is the first oral bisphosphonate available for men with the more comfortable once weekly dosage.

Improved Non-Invasive Biomechanical Evaluation Method for the Virtue of Risedronate

New medicines for treatment of osteoporotic bones have developed. In the previous studies, there were lots of pre-clinical experiments on animals to analyze the virtue of new medicine. However, the previous methods sacrificed a number of animals. They induced lots of expenses and ethical problems. In the present study, to investigate the effect of a medicine for osteoporosis by using in-vivo micro computed tomography (In-vivo Micro-CT, skyscan 1076, skyscan, Belgium) and micro finite element (*FE) analysis, morphological and mechanical characteristic changes of rat bone were detected and tracked. The 8 female Sprague-Dawley rats, used in the experiment, were randomized into 3 groups (Control, Sham and Risedronate group). The Risedronate (actonel, 0.58mg/Kg and 5days/week) for 8 weeks was administered in RIS group. The 4th lumbar vertebrae of rats were scanned by In-vivo Micro-CT with 35*m at week 0 (just before dose) and week 8 (after dose). Three-dimensional (3D) structural parameters were calculated. Simulated compression tests of 3D FE models were carried out to investigate the mechanical characteristics in the whole vertebral bone model of the 4th lumbar vertebra. The change rate of quantity and structure in Risedronate (RIS) group was smaller than that of control (CON) group. The change rate of structural modulus in RIS group was also smaller than that of CON group. This result shows the virtue of risedronate quantitatively as well as qualitatively. The study introduced the improved noninvasive biomechanical evaluation method, combined with In-vivo Micro-CT and *FE analysis, which was more effective and useful than the previous pre-clinical experiments.

Evidence that Treatment with Risedronate in Women with Postmenopausal Osteoporosis Affects Bone Mineralization and Bone Volume

Risedronate is used in osteoporosis treatment. Postmenopausal women enrolled in the Vertebral Efficacy with Risedronate Therapy trial received either risedronate (5 mg/day) or placebo for 3 years. Subjects received calcium and vitamin D supplementation if deficient at baseline. Lumbar spine bone mineral density (BMD) was measured at baseline and at 3 years. Quantitative back-scattered electron imaging (qBEI) was performed on paired iliac crest biopsies (risedronate, n = 18; placebo, n = 13) before and after treatment, and the mineral volume fraction in the trabecular bone was calculated. Combining dual-energy X-ray absorptiometric values with the mineral volume fraction for the same patients allowed us to calculate the relative change in trabecular bone volume with treatment. This showed that the effect on BMD was likely to be due partly to changes in matrix mineralization and partly due to changes in bone volume. After treatment, trabecular bone volume in the lumbar spine tended to increase in the risedronate group (+2.4%, nonsignificant) but there was a significant decrease (-3.7%, P < 0.05) in the placebo group. Calcium supplementation with adequate levels of vitamin D led to an approximately 3.3% increase in mineral content in the bone material independently of risedronate treatment. This increase was larger in patients with lower matrix mineralization at baseline and likely resulted from correction of calcium/vitamin D deficiency as well as from reduced bone remodeling. Combining BMD and bone mineralization density distribution data show that in postmenopausal osteoporosis 3-year treatment with risedronate preserves or may increase trabecular bone volume, unlike placebo. This analysis also allows, for the first time, separation of the contributions of bone volume and matrix mineralization to the increase in BMD.