Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study.

Long-term use of high-dose corticosteroids often results in bone loss, which may lead to osteoporosis-related fractures. This was a multicenter, double-blind study in which 290 ambulatory men and women receiving high-dose oral corticosteroid therapy (prednisone > or = 7.5 mg/day or equivalent) for 6 or more months were randomized to receive placebo, risedronate 2.5 mg/day, or risedronate 5 mg/day for 12 months. All patients received calcium 1 g and vitamin D 400 IU daily. The primary endpoint was lumbar spine bone mineral density (BMD) at month 12. Additional measurements included BMD at the femoral neck and trochanter and the incidence of vertebral fractures. Overall, there were statistically significant treatment effects on BMD at 12 months at the lumbar spine (p < 0.001), femoral neck (p = 0.004), and trochanter (p = 0.010). Risedronate 5 mg increased BMD at 12 months by a mean (SEM) of 2.9% (0.49%) at the lumbar spine, 1.8% (0.46%) at the femoral neck, and 2.4% (0.54%) at the trochanter, whereas BMD was maintained only in the control group. Although not powered to show fracture efficacy, we observed a reduction in the incidence of vertebral fractures of 70% in the combined risedronate treatment groups, relative to placebo (p = 0.042). Risedronate was well tolerated, had a good safety profile, and was not associated with gastrointestinal adverse events. We conclude that risedronate increases BMD and potentially reduces the incidence of vertebral fractures in patients with corticosteroid-induced osteoporosis.     

Treatment of Glucocorticoid-Induced Osteoporosis with Alfacalcidol/Calcium Versus Vitamin D/Calcium

Vitamin D/calcium substitution is generally regarded as an effective first step treatment for glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to evaluate the efficacy of the active vitamin D metabolite alfacalcidol (1α) compared with the native vitamin D₃ in patients with established GIOP with or without vertebral fractures. Patients on long-term corticoid therapy were given either 1 μg alfacalcidol plus 500 mg calcium per day (group A, n = 43) or 1000 IU vitamin D₃ plus 500 mg calcium (group B, n = 42). The two groups were alike in age range, sex ratio, percentages of underlying diseases, average initial bone density values (lumbar spine: mean T-score −3.28 and −3.25, respectively), and rates of vertebral and nonvertebral fractures. During the 3-year study we found a small but significant increase of lumbar spine density in group 1α (+2.0%, P < 0.0001) and no significant changes at the femoral neck. In the D₃ group, there were no significant changes at both sites. At the end of the study, 12 new vertebral fractures had occurred in 10 patients of the group 1α and 21 in 17 patients of the D₃ group. In accordance with the observed fracture rates, the alfacalcidol group showed a significant decrease in back pain (P < 0.0001) whereas no change was seen in the vitamin D group. We conclude that with the doses used in this trial, alfacalcidol is superior to vitamin D in the treatment of established GIOP.     

鲑鱼降钙素在骨质疏松性椎体压缩骨折椎体后凸成形术后的应用

目的观察鲑鱼降钙素对骨质疏松性椎体压缩骨折行椎体后凸成形术后骨密度及腰背痛症状的改善情况。方法将行椎体后凸成形术后的骨质疏松性椎体压缩骨折患者79例分成两组,鲑鱼降钙素组44例,予以鲑鱼降钙素肌肉注射,术后每天1次100IU,连用3 d后,改为50 IU隔天1次,连用1个月,间歇1个月后再重复,共半年,同时加服维D2磷葡钙;对照组35例,单纯口服维D2磷葡钙,疗程半年。两组治疗前后均测定腰1～腰4椎体及股骨颈骨密度(BMD);并观察患者腰背痛的情况。结果:鲑鱼降钙素组有6例因肌注降钙素出现面部潮红和皮肤瘙痒等反应停止疗程,其余38例和对照组35例得到了随访。鲑鱼降钙素组腰椎及股骨颈BMD较治疗前明显升高(P<0.01),对照组各部位骨密度较治疗前无明显改变(P>0.01)。鲑鱼降钙素组没有病例再次出现腰背痛,而对照组在半年内有7例再次出现腰背痛,经腰椎MRI证实发生其他节段的椎体压缩骨折。结论:鲑鱼降钙素与钙剂联合治疗行椎体后凸成形术后的骨质疏松性椎体压缩骨折患者,可以提高患者的骨量,降低再骨折的风险。     

The effect of intranasal salmon calcitonin therapy on bone mineral density in idiopathic male osteoporosis without vertebral fractures--an open label study

The aim of this study was to examine the effect of intranasal salmon calcitonin therapy on bone mineral density (BMD) in idiopathic male osteoporosis without vertebral fractures. We conducted a randomized, open label, controlled trial in 71 male patients (mean age 59 +/- 6 years) suffering from idiopathic osteoporosis (femoral neck T-score < -2.5) without vertebral deformity. Patients in the control group (n = 31) received 400 IU Vitamin D + 1000 mg elemental calcium daily while the treatment group (n = 40) received 400 IU Vitamin D, 1000 mg elemental calcium plus 200 IU calcitonin nasal spray daily during alternate months. The study period was 18 months. Compared to controls, nasal calcitonin was associated with significant increases in bone mineral density at the lumbar spine (+3.5 +/- (-4.3%) vs. +0.83 +/- 6.4%, P = 0.04) and the femoral neck (+3.2 +/- 3.9% vs. +0.68 +/- 5.7%, P = 0.004). No significant difference was observed at the radius between the treatment groups (+1.4 +/- 8.8% vs. +1.4 +/- 10.9%, P = 0.98). Treatment was well tolerated with no premature discontinuations or significant side effects compared to the control group. We conclude that 200 IU salmon calcitonin nasal spray used daily, intermittently proved to be an effective and safe therapy in male idiopathic osteoporosis.     

Nandrolone decanoate and intranasal calcitonin as therapy in established osteoporosis

This study used a randomized, 2 × 2 factorial design to evaluate over 2 years the effect of intranasal salmon calcitonin and intramuscular nandrolone decanoate on bone mass in elderly women with established osteoporosis. The study was double masked in relation to calcitonin and open in relation to nandrolone decanoate. One hundred and twenty-three women aged 60–88 years who had sustained a previous osteoporotic fracture, or had osteopenia, were recruited through an outpatient clinic. Women were assigned to one of four groups: (1) daily placebo nasal spray, (2) 400 IU intranasal calcitonin daily, (3) 20 intramuscular injections of 50 mg nandrolone decanoate (given as two courses of 10 injections) plus placebo nasal spray, or (4) 20 injections of 50 mg nandrolone decanoate plus 400 IU intranasal calcitonin daily. All subjects received 1000 mg calcium supplementation daily. Outcomes measured included changes in bone mineral density (BMD) at the lumbar spine, as measured by dual-energy quantitative computed tomography (DEQCT), in BMD of the proximal femur, and BMD and bone mineral content (BMC) of the lumbar spine and forearm, as measured by dual-energy X-ray absorptiometry (DXA). Significant positive changes from baseline in DXA BMC at the lumbar spine were observed over 2 years in the calcitonin group (5.0±1.9%, mean ± SE) and in the nandrolone deconate group (4.7±1.9%) but not in the placebo group (1.1±2.2%) or the combined therapy group (0.7±1.8%). Modelling based on the 2×2 factorial design revealed that nandrolone decanoate was associated with a 3.8±1.8% (p<0.05) gain in DXA BMD at the proximal femur. Modelling also revealed that calcitonin treatment was associated with a loss of 11.5±4.7% in DEQCT BMD at the lumbar spine and a loss of 3.7±1.8% in DXA BMD at the proximal femur (p<0.05). There was in vivo antagonism between the two medications of 7.9±3.9% for DXA BMC at the lumbar spine. Both agents caused positive changes from baseline in lumbar spine BMC. Nandrolone decanoate had beneficial effects on BMD at the proximal femur. This dose of intranasal calcitonin was associated with deleterious effects on trabecular BMD at the lumbar spine and total BMD at the proximal femur. There may be significant clinical antagonism between these two medications.     

Prevention and treatment of glucocorticoid-induced osteoporosis with active vitamin D<Subscript>3</Subscript> analogues: a review with meta-analysis of randomized controlled trials including organ transplantation studies

The aim of this review with meta-analysis was to determine if there is a rationale to use activated forms of vitamin D₃ to treat or prevent glucocorticoid-induced osteoporosis, and to compare the effect of active vitamin D₃ metabolites with that of other anti-osteoporosis therapies. We performed a systemic search using MEDLINE/PubMed (1966–2003). Animal studies and clinical trials involving humans with data on therapy to treat or prevent glucocorticoid-induced osteoporosis with active vitamin D₃ analogues were included. Animal studies and basic research studies with active vitamin D₃ were reviewed (qualitative review). Meta-analysis (quantitative review) on clinical trials (including organ transplantation studies) was performed with percent change in lumbar spine bone mineral density or bone mineral content as the primary outcome measure; the secondary outcome measure was incidence of vertebral fractures. Fifty-four articles were found. Animal and basic research studies showed that active vitamin D₃ analogues can inhibit bone loss during treatment with glucocorticoids. Concerning the effect on bone mineral density, the pooled effect size of active vitamin D₃ analogues compared with no treatment, placebo, plain vitamin D₃ and/or calcium was 0.35 (95% confidence interval (CI) 0.18, 0.52). Compared with bisphosphonates, the pooled effect size was –1.03 (95% CI –1.71, –0.36). The pooled estimate of the relative risk for vertebral fractures of active vitamin D₃ analogues compared with no treatment, placebo, plain vitamin D₃ and/or calcium was 0.56 (95% CI 0.34, 0.92) and compared with bisphosphonates it was 1.20 (95% CI 0.32, 4.55). Active vitamin D₃ analogues not only preserve bone during glucocorticoid therapy more effectively than no treatment, placebo, plain vitamin D₃ and/or calcium, but are also more effective in decreasing the risk of vertebral fractures. Bisphosphonates, however, are more effective in preserving bone and decreasing the risk of vertebral fractures than active vitamin D₃ analogues.     

Total and regional bone mineral content and fracture rate in postmenopausal osteoporosis treated with salmon calcitonin: A prospective study

Seventy-two postmenopausal osteoporotic women having more than one nontraumatic vertebral crush fracture were studied. Thirty-six of them, aged 68.8±1.2 years (18±4 YSM-years since menopause), were treated with 100 IU/day of salmon calcitonin i.m. plus 500 mg of elemental calcium for 10 days each month. The remaining 36 patients, aged 69.6±1.4 years (19±3 YSM), were given only 500 mg of elemental calcium for 10 days each month. All patients underwent clinical and analytical evaluation every 3 months. Radiological evaluation, assessment of vertebral deformities, and metacarpal radiogrammetry were done every 6 months. Densitometric measurements of total and regional bone mass were made every 12 months. At 24 months, the calcitonin group showed a 60% reduction in the number of new fractures and the group receiving only calcium had a 45% increase (P<0.001). The incidence of vertebral fractures was 0.07 per patient-year in the group treated with calcitonin and 0.45 per patient-year in the group treated with calcium (P<0.001). At 2 years, the calcitonin group showed a 12% increase in cortical bone mass on metacarpal radiogrammetry, a 16% increase in the axial skeleton on trunk densitometry, a 3.5% increase in total body bone mineral content, a 30.7% increase in pelvic bone mineral content, and a 6.2% increase in arm bone mineral content (all P<0.001). In the group treated with calcium alone there was a loss of bone mass in every region. These findings suggest that salmon calcitonin is effective in the treatment of osteoporosis and show that it acts on cortical and trabecular bone.     

Effects of 4-year treatment with once-weekly clodronate on prevention of corticosteroid-induced bone loss and fractures in patients with arthritis: evaluation with dual-energy X-ray absorptiometry and quantitative ultrasound

The aim of this placebo-controlled study was to determine whether once-weekly clodronate could prevent osteoporosis in patients with arthritis at the start of corticosteroid therapy. One hundred sixty-three patients, 18 to 90 years of age, with rheumatoid or psoriatic arthritis, were randomly assigned to receive either clodronate (100 mg im/week) plus calcium and vitamin D (1000 mg and 800 UI, respectively) or calcium and vitamin D alone. Patients had started therapy with prednisone or its equivalent within the previous 100 days and had bone mineral density <2.5 SD below mean young normal values at the lumbar spine or femoral neck. The primary outcome was the difference between the two treatment groups at months 12, 24, 36, and 48 in the mean percentage change from baseline in the bone mineral density of the lumbar spine, femur (neck and total), and total body. Secondary measurements included changes in the stiffness index evaluated by ultrasound measurements and the rate of new vertebral fractures. The bone density and stiffness did not change significantly in the clodronate plus calcium and vitamin D group, whereas it declined significantly in the calcium plus vitamin D group. The difference between treatment groups at 48 months in the mean change from baseline was 8.78 +/- 1.4% for the lumbar spine (P < 0.01), 7.31 +/- 1.12% for the femoral neck (P < 0.01), 7.92 +/- 1.93% for the trochanter (P < 0.01), 8.39 +/- 1.80% for total femur (P < 0.01), 6.94 +/- 1.09% for total body (P < 0.01), and 9.38 +/- 2.21% for stiffness of os calcis (P < 0.01). Depending on the skeletal regions evaluated, 85 to 98% of patients treated with clodronate had a densitometric change lower than the lowest significant densitometric difference. One hundred percent of patients treated with calcium plus vitamin D had a densitometric decrease greater than the lowest significant difference. The relative risk of vertebral fractures and multiple vertebral fractures in the clodronate group compared to the calcium plus vitamin D group was 0.63 (0.35-0.98, 95% CI) and 0.25 (0.15-0.91, 95% CI), respectively. We concluded that pulsatory administration of im clodronate once weekly is a safe therapy for preventing corticosteroid induced osteoporosis in patients with arthritis.     

A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: the Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) trial

The Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) study was a randomized, double‐blind, double‐dummy, active‐ and placebo‐controlled, multiple‐dose, phase 3 study to assess the efficacy and safety of oral recombinant calcitonin for treatment of postmenopausal osteoporosis. A total of 565 women age 46 to 86 (mean 66.5) years were randomized (4:3:2) to receive oral recombinant salmon calcitonin (rsCT) tablets (0.2 mg/d) plus placebo nasal spray, synthetic salmon calcitonin (ssCT) nasal spray (200 IU/d) plus placebo tablets, or placebo (placebo tablets plus placebo nasal spray), respectively for 48 weeks. All women received calcium (≥1000 mg/d) and vitamin D (800 IU/d). Women randomized to oral rsCT had a mean ± SD percent increase from baseline in lumbar spine bone mineral density (BMD) (1.5% ± 3.2%) that was greater than those randomized to ssCT nasal spray (0.78% ± 2.9%) or placebo (0.5% ± 3.2%). Lumbar spine BMD change in those receiving nasal calcitonin did not differ from placebo. Oral rsCT treatment also resulted in greater improvements in trochanteric and total proximal femur BMD than ssCT nasal spray. Reductions in bone resorption markers with oral rsCT were greater than those observed in ssCT nasal spray or placebo recipients. Approximately 80% of subjects in each treatment group experienced an adverse event, the majority of which were mild or moderate in intensity. Gastrointestinal system adverse events were reported by nearly one‐half of women in all treatment groups and were the principal reason for premature withdrawals. Less than 10% of women experienced a serious adverse event and no deaths occurred. Overall, oral rsCT was superior to nasal ssCT and placebo for increasing BMD and reducing bone turnover. Oral rsCT was safe and as well tolerated as ssCT nasal spray or placebo. Oral calcitonin may provide an additional treatment alternative for women with postmenopausal osteoporosis. © 2012 American Society for Bone and Mineral Research.     

Fluoride Salts are no Better at Preventing New Vertebral Fractures than Calcium-Vitamin D in Postmenopausal Osteoporosis: The FAVOStudy

Although fluoride salts have been shown to be capable of linearly increasing spinal bone mineral density (BMD) in postmenopausal osteoporosis, the effects of this gain in density on the vertebral fracture rate remain controversial. We conducted a 2-year multicenter, prospective, randomized, double-masked clinical trial in 354 osteoporotic women with vertebral fractures (mean age 65.7 years). They received either fluoride (208 patients), given as sodium fluoride (50 mg/day) or as monofluorophosphate (200 mg/day or 150 mg/day), or a placebo (146 patients). All patients received daily supplements of 1 g of calcium (Ca) and 800 IU of vitamin D₂ (D). A 1-year open follow-up on Ca-D was obtained in 124 patients. After 2 years the fluoride group and the Ca-D group had increased their lumbar BMD by 10.8% and 2.4% respectively (p = 0.0001). However, the rate of patients with at least one new vertebral fracture, defined by semiquantitative assessment and evaluable on an intention-to-treat basis in 89% of patients, was similar in the fluoride groups and the Ca-D group. No difference between the three fluoride regimens was found. The percentage of patients with nonvertebral fractures was not different in the fluoride and Ca-D groups (1.9% and 1.4% respectively for hip fractures). A lower limb pain syndrome occurred more frequently in the fluoride groups. In the 124 patients followed for 1 year after cessation of fluoride therapy, the percentage of patients with at least one new vertebral fracture after 36 months was identical to the percentages in the previous fluoride group and the Ca-D group. We conclude that flouride-Ca-D regimen was no more effective that Ca-D supplements for the prevention of new vertebral fractures in women with postmenopausal osteoporosis.     

降钙素治疗骨质疏松症骨质量病变的研究

目的研究降钙素在骨质疏松症治疗中对骨密度bonemineraldensityBMD、骨强度及骨质疏松脆性骨折发生率的作用。方法为期1年的单中心、前瞻性、随机研究135例原发性骨质疏松症女性患者随机分成降钙素 钙剂组和钙剂组,进行开放、对比研究。降钙素 钙剂组66例鲑鱼降钙素50IU,肌内注射,第1周每天1次,第2周隔日1次,以后每周2次;同时口服元素钙600mg每天1次。钙剂组69例元素钙600mg每天1次。治疗前后分别进行血清钙、磷、碱性磷酸酶、骨钙素、尿羟脯氨酸、双能X线BMD和超声骨强度测量以及脊椎胸腰段正、侧位X线片比较。结果治疗1年后,降钙素 钙剂组53例获随访,与治疗前比较,腰椎BMD上升约1%P<0.05,髋部BMD无明显变化,桡骨和胫骨骨强度均明显改善;钙剂组59例获随访,腰椎、髋部BMD和桡骨、胫骨骨强度均较治疗前下降P<0.05。两组治疗前后各项生化检测指标无明显变化,骨质疏松脆性骨折的发生率钙剂组明显高于降钙素 钙剂组。结论降钙素治疗骨质疏松症有良好作用,不仅能有效地缓解骨痛,还能确实提高骨质量,降低骨质疏松脆性骨折的发生率。     

Effects of Risedronate Treatment on Bone Density and Vertebral Fracture in Patients on Corticosteroid Therapy

Men and women (n = 518) receiving moderate-to-high doses of corticosteroids were enrolled in two studies with similar protocols and randomly assigned to receive either placebo or risedronate (2.5 or 5 mg) for 1 year. All patients received daily calcium supplementation (500–1000 mg), and most also received supplemental vitamin D (400 IU). The primary endpoint was the difference between the placebo and active groups in lumbar spine bone mineral density (BMD) at 1 year; changes in BMD at other sites, biochemical markers of bone turnover, and the incidence of vertebral fractures were also assessed. In the overall population, the mean (SE) lumbar spine BMD increased 1.9 ± 0.38% from baseline in the risedronate 5 mg group (P < 0.001) and decreased 1.0 ± 0.4% in the placebo group (P= 0.005). BMD at the femoral neck, trochanter, and distal radius increased or was maintained with risedronate 5 mg treatment, but decreased in the placebo group. Midshaft radius BMD did not change significantly in either treatment group. The difference in BMD between the risedronate 5 mg and placebo groups was significant at all skeletal sites (P < 0.05) except the midshaft radius at 1 year. The 2.5 mg dose also had a positive effect on BMD, although of a lesser magnitude than that seen with risedronate 5 mg. A significant reduction of 70% in vertebral fracture risk was observed in the risedronate 5 mg group compared with the placebo group (P= 0.01). Risedronate was efficacious in both men and women, irrespective of underlying disease and duration of corticosteroid therapy, and had a favorable safety profile, with a similar incidence of upper gastrointestinal adverse events in the placebo and active treatment groups. Daily treatment with risedronate 5 mg significantly increases BMD and decreases vertebral fracture risk in patients receiving moderate-to-high doses of corticosteroid therapy. Received: 11 October 1999 / Accepted: 1 May 2000 / Online publication: 27 July 2000     

Salmon calcitonin in the prevention of bone loss at perimenopause

The objective of this study was to determine whether intranasal salmon calcitonin prevents physiological bone loss at perimenopause. A double-blind study of 120 perimenopausal women without present or past disease or medication that could affect bone metabolism were studied. The subjects were randomized in two groups and provided with nasal spray bottles containing either placebo (excipient only) or active compound (excipient plus 50 international units (IU) salmon calcitonin per dose). Subjects took one puff from the nasal spray in each nostril every morning. All subjects took one soluble tablet of calcium (1000 mg) per day. Serum biochemistry, dual-energy X-ray absorptiometry of lumbar spine and proximal femur, quantitative computed tomography of lumbar spine, and single photon attenuation of forearm were used to evaluate bone mineral density (BMD). There were no differences in demographic characteristics or hormone status at entry. No fractures were recorded during the study period. Serum calcium increased and serum dihydroxyvitamin D and osteocalcin decreased in both groups. There was no difference in biochemical parameters between the groups. The BMD of upper femur did not change during the study, but it was decreased in the lumbar spine in both groups. The mineral content of distal radius increased in both groups. In conclusion, nasal salmon calcitonin, 100 IU daily, has no protective effect on bone mass and does not modify bone metabolism at perimenopause.     

A comprehensive review of treatments for postmenopausal osteoporosis

 The aim of this review is to assess the efficacy of treatments for postmenopausal osteoporosis in women with low bone mass or with an existing vertebral fracture. We searched the literature for studies (randomized, double-masked, placebo-controlled and prospective) that reported on drugs registered in Europe or North America. We included 41 reports on 12 agents. To assess the consistency among the studies for each drug, we plotted the percent change in bone mineral density (BMD) for the control group against the percent change in BMD for the treated group for lumbar spine and femoral neck. We used methods of cluster analysis to determine consistency among the studies. For each agent we summarized the relative risk for vertebral fracture (patients with new fracture) and for hip fractures. The duration of the studies ranged from 1 to 4.3 years. The proportion of patients who discontinued treatment ranged from 4% to 80%. Most of the studies reported on change in BMD. Twenty-six studies (10 drugs) provided data on new vertebral fractures and 12 (6 drugs) on hip fractures. Apart from fluoride effects on spine BMD, increases in BMD with bisphosphonates were greater than those seen with the remaining treatments. Generally, for each agent the changes in BMD (relative to placebo) were consistent among the studies. The exceptions were calcitriol and calcitonin for changes in BMD of the spine and of the femoral neck. Alendronate, calcitonin, risedronate and raloxifene caused significant reductions in the risk of vertebral fractures. Alendronate, risedronate or the combination of calcium plus vitamin D had a significant effect on the risk of hip fracture. Most therapies are effective in increasing BMD; some decrease the risk of vertebral fracture. For hip fracture, alendronate and risedronate reduce the risk in women with osteoporosis, and calcium and vitamin D reduce the risk in institutionalized patients. Received: 15 October 2001 / Accepted: 18 July 2002 Acknowledgement We acknowledge the invaluable help of J. Jeger, MD, for useful discussion, D. Thompson, PhD, for statistical advice, and D. Koch for data collection. We thank Mrs M. Perez for secretarial assistance. This work was partially supported by a grant from the Merck Sharp and Dohme-Chibret Company (Glattbrugg, Switzerland).     

Combined Vertebral Assessment and Bone Densitometry Increases the Prevalence and Severity of Osteoporosis in Patients Referred to DXA Scanning

We performed a retrospective study to assess if vertebral fracture assessment (VFA) after routine bone mineral density (BMD) measurement on a dual-energy X-ray absorptiometry (DXA) machine had increased the number of patients diagnosed with osteoporosis and revealed previous unknown incident vertebral fractures. A total of 3275 patients were referred to bone densitometry by DXA to be screened for osteoporosis or evaluation of ongoing antiosteoporotic treatment. All spine X-rays obtained at our hospital from the same patients in the period from 3 mo before to 3 mo after the date of DXA scans were reviewed. Among the 3275 patients, 85% were females and 15% were males. In total, 68% of the patients had normal BMD, and 32% had osteoporosis. Vertebral fractures diagnosed by VFA were seen in 7.9% patients, of which 3.2% had normal BMD and 4.8% had osteoporosis assessed by BMD. The relative number of patients diagnosed with osteoporosis increased 9.79% and in absolute terms from 32.4% to 35.6% of patients referred to DXA. Addition of VFA to routine BMD measurement increased clinically significant the number of patients diagnosed with osteoporosis as well as the number of patients with fractures and thereby altered the severity and prognosis.     

A three-year comparative trial in osteoporosis treatment: Effect of combined alfacalcidol and elcatonin

The effect of agents commonly used for osteoporosis treatment in Japan—calcium, alfacalcidol (1α-hydroxyvitamin D₃), elcatonin (eel calcitonin derivative), and an alfacalcidol-elcatonin combination—on lumbar spine bone mineral density (BMD) was assessed in 136 subjects aged 51–83 years with various degrees of osteopenia or osteoporosis, divided into five groups approximately matched for age and BMD over a period of 3 years. Lumbar spine BMD decreased by about 3.5% without treatment but was maintained at approximately baseline level on elcatonin. Oral administration of 900mg/day calcium as AAA Ca (active absorbable algae calcium) or 1μg/day alfacalcidol increased lumbar BMD by 4.5% or 3.7%, respectively, after 3 years. Combined use of alfacalcidol and elcatonin was most effective, increasing the BMD by 8.0% after 3 years. Extremely low calcium and vitamin D intake in Japan with consequent low calcitonin secretion may be responsible for the favorable effects. Alfacalcidol, an active form of vitamin D, and elcatonin acting through different mechanisms may act synergistically on bone to increase BMD.     

New or worsening lumbar spine vertebral fractures increase lumbar spine bone mineral density and falsely suggest improved skeletal status.

Changes in lumbar spine bone mineral density (BMD) are determined by follow-up dual-energy x-ray absorptiometry (DXA) assessments. Inclusion of new or worsening vertebral fractures in follow-up measurements may increase BMD. To test this hypothesis, we examined pooled data from the placebo groups of two clinical trials that involved postmenopausal women with osteoporosis. DXA measurements of lumbar spine BMD, bone mineral content (BMC), and area were obtained at baseline and at two years in the Multiple Outcomes of Raloxifene Evaluation (MORE) Trial and at baseline and study endpoint in the Fracture Prevention Trial. In these trials, fractured vertebrae identified by expert radiologists during posterioranterior (PA) spine DXA assessment were excluded from the BMD assessment. Lateral spine radiographs were graded using a semi-quantitative (SQ) scale. Most new or worsening vertebral fractures (84%) diagnosed from lateral spine radiographs were not identified by PA spine DXA. While the follow-up BMD of vertebrae without new or worsening fractures did not change significantly, each unit increase in SQ grade was associated with an approximate 7.0% increase in the BMD of affected vertebrae (p < 0.001). Increases in BMD were highly correlated with increases in BMC (r = 0.87, p < 0.001). Inclusion of new or worsening vertebral fractures increased PA spine BMD measurements at follow-up, with the impact being related to the magnitude of change in SQ score. It is difficult to reliably identify vertebral fractures from PA spine DXA assessments. Inclusion of new or worsening vertebral fractures in follow-up DXA measurements may falsely suggest an improvement in spine BMD. Our suggestion is to perform lateral spine imaging concurrently with any assessment of PA spine BMD in patients who, in the opinion of the health care provider, may have vertebral fractures.     

Calcitonin and bisphosphonates treatment in bone loss after liver transplantation

Osteopenia is a major complication of orthotopic liver transplantation (OLT). However, no effective therapy for bone disease has been defined. We have studied vertebral bone mineral density (VMD) and fasting serum markers of bone formation [bone gla protein (BGP), procollagen I carboxyterminal peptide (PICP)] and metabolism (serum Ca, P, intact parathyroid hormone (iPTH), 25OHD₃ and 1,25(OH)₂D₃) in 120 patents after OLT. VMD was measured by dual-energy X-ray absorptiometry (DXA) using a Hologic QDR 1000 densitometer on two occasions, 12 months apart. Patients with OLT had a VBD significantly lower compared with age- and sexed-matched Spanish controls (P<0.05). Prevalence of osteoporosis (Z score below-2 SD) was 35.8%. Serum BGP (8.6±0.7 ng/ml) and PICP (222.9±81.9 ng/dl) were higher than those of controls. However, serum calcium, phosphorus, iPTH, 25OHD₃, and 1,25(OH)₂D₃ were within normal range. Patients with osteoporosis were randomly treated with 40 IU/day of calcitonin i.m. (Diatin, Ferrer Int. Laboratories) (n=17) or 400 mg p.o., 15 days every 3 months, of sodium ethiodronate (Difosfen, Rubio Laboratories) (n=23). All patients received 500 mg/12 hours of elemental calcium p.o. After 12 months of treatment, a significant increment of vertebral mineral density (VMD) was observed (6.4% and 8.2%, respectively). Serum BGP and PICP values remained elevated without a difference between the two drugs. Our results indicate that antiresorptive drugs may be of benefit in the high turnover osteoporosis of OLT recipients.     

Positive effect of alendronate on bone mineral density and markers of bone turnover in patients with rheumatoid arthritis on chronic treatment with low-dose prednisone: a randomized, double-blind, placebo-controlled trial

Introduction Alendronate has been described to have a bone-sparing effect in patients treated with moderate and high dosages of prednisone for heterogeneous diseases, however no data are available on groups of patients with the same underlying diseases who receive chronic low-dose prednisone treatment. The objective of the investigation reported here was, therefore, to study the effect of alendronate on bone mineral density (BMD) of the lumbar spine and hips in patients with rheumatoid arthritis (RA) who are on chronic low-dose prednisone treatment. Methods A total of 163 patients with RA, according to the ACR-criteria, were enrolled in a double-blind, placebo-controlled trial. The patients were treated with low-dose prednisone (≤10 mg/day) for at least 3 months. The patients were randomized to receive daily doses of alendronate or placebo: men and premenopausal women received 5 mg alendronate (or placebo) daily; postmenopausal women received 10 mg alendronate (or placebo) daily. All patients received daily calcium (500 mg, or 1000 mg, depending on baseline dietary calcium intake) and vitamin D₃ (400 IU) supplementation. BMD of the lumbar spine (L1–L4) and the (total) hip was measured at baseline and after 6 and 12 months. The primary endpoint was change in BMD of the lumbar spine after 12 months (ITT). At baseline and after 3 and 12 months, serum bone-specific alkaline phosphatase (BAP) and urinary excretion of N-telopeptide (NTX) were measured. Radiographs of the thoracic and lumbar spine were made at baseline and after 12 months and subsequently scored for vertebral deformities. Results The groups were comparable at baseline in age, gender, daily dosage of prednisone, BMD at the spine and the hip and markers of bone turnover, while the number of patients with prevalent vertebral deformities was slightly higher in the alendronate-treated patients (54% versus 39%, not significant). After 12 months, BMD at the lumbar spine had increased by 3.7% in the alendronate-treated patients and decreased by –1.0% in the placebo-treated patients (p<0.0001); at the hip, the changes were +1.0% and –0.1%, respectively (not significant). After 3 months, serum BAP had decreased by 16.9% in the alendronate group versus 3.3% in the placebo group (p=0.0005), while urinary NTX had decreased by 46.4% in the alendronate group versus 12.1% in the placebo group (p<0.0001). After 12 months, no statistically significant difference was found between the groups with respect to number of patients with incident vertebral or non-vertebral fractures. Adverse effects were relatively common in these patients with severe RA: adverse effects were observed in 68% of the alendronate-treated patients and in 73% of the placebo patients (not significant), while serious adverse events were observed in 13% and 17%, respectively (not significant). Conclusion We observed a favourable effect of alendronate on the BMD of the lumbar spine and on the markers of bone turnover in patients with RA treated with low-dose prednisone. These data support the conclusion that the prescribing of alendronate is not only beneficial in patients treated with high-dose prednisone but also in RA patients chronically treated with low-dose prednisone. This trial was financially supported by a grant from MSD, The Netherlands     

Combined Calcium and Vitamin D3 Supplementation in Elderly Women: Confirmation of Reversal of Secondary Hyperparathyroidism and Hip Fracture Risk: The Decalyos II Study

Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people. Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures, as proved by Decalyos I. Decalyos II is a 2-year, multicenter, randomized, double-masked, placebo-controlled confirmatory study. The intention-to-treat population consisted of 583 ambulatory institutionalized women (mean age 85.2 years, SD = 7.1) randomized to the calcium–vitamin D₃ fixed combination group (n= 199); the calcium plus vitamin D₃ separate combination group (n= 190) and the placebo group (n= 194). Fixed and separate combination groups received the same daily amount of calcium (1200 mg) and vitamin D₃ (800 IU), which had similar pharmacodynamic effects. Both types of calcium-vitamin D₃ regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent, with levels returning within the normal range after 6 months. In a subgroup of 114 patients, femoral neck bone mineral density (BMD) decreased in the placebo group (mean =–2.36% per year, SD = 4.92), while remaining unchanged in women treated with calcium-vitamin D₃ (mean = 0.29% per year, SD = 8.63). The difference between the two groups was 2.65% (95% CI =–0.44, 5.75%) with a trend in favor of the active treatment group. No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis. The relative risk (RR) of HF in the placebo group compared with the active treatment group was 1.69 (95% CI = 0.96, 3.0), which is similar to that found in Decalyos I (RR = 1.7; 95% CI = 1.0, 2.8). Thus, these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D₃ in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women. Received: 23 March 2001 / Accepted: 28 October 2001