Alendronate treatment of established primary osteoporosis in men: 3-year results of a prospective,comparative, two-arm study

Our trial was a 3-year, open-label, prospective, comparative, clinical study comparing the effects of oral alendronate (ALN), 10 mg daily, and alfacalcidol (AC), 1 g daily, on bone mineral density (BMD), fracture events, height, back pain, safety and tolerability in 134 men with established primary osteoporosis. All men received 500 mg calcium daily. BMD was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry (DXA). Spine radiographs were obtained at baseline and every 12 months thereafter, and were evaluated by a radiologist blinded to treatment assignment. At 3 years, AC-treated patients showed a significant mean increase of 3.5% in lumbar spine BMD, compared with a mean increase of 11.5% in men receiving ALN (p<0.0001 between groups). The corresponding increases in femoral neck BMD were 2.3% and 5.8% for the AC and ALN groups, respectively (p=0.0015 between groups). Over 3 years, new vertebral fractures occurred in 24.2% of the AC-treated patients and in 10.3% of the ALN-treated patients (p=0.040). ALN-treated patients also had a significantly lower height loss. There were no between-group differences regarding nonvertebral fractures or changes in back pain. Both therapies were well tolerated, with a compliance rate >90%. We conclude that although AC has significant effects on BMD, ALN has greater effects on BMD and fracture efficacy.     

Alendronate in the treatment of primary hyperparathyroid-related osteoporosis: a 2-year study

We investigated the effect of alendronate on calcium, PTH, and bone mineral density in 27 female and 5 male patients with primary hyperparathyroidism. The treatment group [n = 14; T score < or = -2.5 SD at the femoral neck (FN) or T < or = -1.0 SD plus previous nonvertebral fracture] was given alendronate 10 mg/d for 24 months. The second group (n = 18; T score > -2.5 SD at the FN) was untreated. Biochemistry was repeated at 1.5, 3, 6, 12, 18, and 24 months, and dual-energy x-ray absorptiometry at 12 and 24 months. There were no significant between-group baseline differences in calcium, creatinine, or PTH. Alendronate-treated patients gained bone at all sites [lumbar spine (LS), 1 yr gain, +7.3 +/- 1.7%; P < 0.001; 2 yr, +7.3 +/- 3.1%; P = 0.04). Untreated patients gained bone at the LS over 2 yr (+4.0 +/- 1.8%; P = 0.03) but lost bone elsewhere. Calcium fell nonsignificantly in the alendronate group between baseline (2.84 +/- 0.12 mmol/liter) and 6 wk (2.76 +/- 0.09 mmol/liter), with a nonsignificant rise in PTH (baseline, 103.5 +/- 14.6 ng/liter; 6 wk, 116.7 +/- 15.6 ng/liter). By 3 months, values had reverted to baseline. In primary hyperparathyroidism, alendronate is well tolerated and significantly improves bone mineral density at the LS (with lesser gains at FN and radius), especially within the first year of treatment. Short-term changes in calcium and PTH resolve by 3 months.     

阿仑膦酸钠治疗男性原发性骨质疏松症临床研究

目的 探讨骨吸收抑制剂阿仑膦酸钠对男性原发性骨质疏松症骨密度和骨转换生化指标的影响.方法 2005年1月至2007年1月前瞻性纳入北京协和医院诊断的20例男性原发性骨质疏松症患者,以20名正常男性为对照.骨质疏松症患者每周服用阿仑膦酸钠70 mg,且每日服用钙尔奇D 1片,疗程为18个月.每6个月采用双能x线骨密度仪测量腰椎和股骨近段骨密度,每3个月测量骨形成指标碱性磷酸酶和骨吸收指标Ⅰ型胶原羧基末端肽.正常男性不予干预,研究开始时和18个月时检查腰椎和股骨近端骨密度.结果 骨质疏松症组治疗前骨密度明显低于正常对照组.阿仑膦酸钠组治疗18个月时,与治疗前比较,腰椎、股骨颈、大转子、全髋和股骨干骨密度值增加6.3%、2.5%、5.8%、3.5%及4.2%(P均<0.05).骨转换生化指标碱性磷酸酶(ALP)和CTX治疗6个月时即显著下降,此后维持在较低水平,治疗18个月后ALP降低33.6%,CTX下降66.7%(P均<0.01).骨吸收指标较骨形成指标下降更明显.患者对阿仑膦酸钠的耐受性良好.正常对照组骨密度和血ALP在18个月期间无明显变化.结论 与对女性骨质疏松症患者疗效相似,阿仑膦酸钠能够明显增加男性原发性骨质疏松症患者的骨密度、降低骨转换生化指标,且安全性良好.     

Sustained efficacy of risedronate in men with primary and secondary osteoporosis: results of a 2-year study

The aim of this study was to assess the effect of treatment with risedronate 5 mg daily relative to control in men with primary or secondary osteoporosis over 2 years. Osteoporosis is a common condition in men that can have serious clinical consequences. In an earlier interim report, we found that 1 year of risedronate therapy resulted in significant increases in bone mineral density (BMD) and a significant reduction in vertebral fractures compared to control in men with osteoporosis. We conducted an open-label, prospective, match-control trial on men with primary or secondary osteoporosis in a single center, outpatient setting. Men with primary or secondary osteoporosis, as defined by a baseline lumbar spine BMD T-score ≤ −2.5 and a baseline femoral neck BMD T-score ≤ 2.0, were eligible for this study. Patients who had been treated with bisphosphonates or fluoride within the last 12 months were excluded. A total of 316 men were randomized to risedronate (n = 158) or control (n = 158). Patients were stratified by the presence of prevalent vertebral fractures at baseline and case by case allocated to either daily treatment with risedronate 5 mg daily plus calcium (1,000 mg) and vitamin D (800 IU) or to a control group (daily alfacalcidol (1 μg) plus calcium (500 mg) for those with prevalent vertebral fractures; daily vitamin D (800 IU) plus calcium (1,200 mg) for those without previous vertebral fractures). Primary study end points were identified prior to study initiation as the incidence of new vertebral fractures and changes in BMD at the lumbar spine, femoral neck, and total hip. Other end points included incidence of nonvertebral fractures and change in body height and back pain. Compared to control, the incidence of new vertebral fractures was significantly reduced in the risedronate 5 mg daily group at 2 years [14/152 (9.2%) for risedronate vs. 35/148 (23.6%) for control (61% risk reduction; P = 0.0026)]. Treatment with risedronate 5 mg daily also resulted in significant improvements in BMD at 2 years at all three skeletal sites (lumbar spine, 6.5 vs. 2.2%; femoral neck, 3.2 vs. 0.6%; total hip, 4.4 vs. 0.4% (P < 0.001 for all treatment comparisons). Significant reductions in the incidence of nonvertebral fractures (11.8 vs. 22.3%; P = 0.032), average loss in height, and back pain were also observed in risedronate-treated patients relative to control. In this 2-year study, daily 5 mg risedronate significantly reduced the risk of vertebral and nonvertebral fractures, improved BMD, decreased height loss, and reduced back pain in men with osteoporosis. Efficacy was sustained over 2 years; a consistent 60–61% risk reduction in vertebral fractures was observed at 1 and 2 years, respectively. These data demonstrate that daily risedronate is effective long-term therapy for men with primary or secondary osteoporosis.     

Efficacy of risedronate in men with primary and secondary osteoporosis: results of a 1-year study

Osteoporosis is prevalent in men with an estimated one in eight men older than 50 years suffering from osteoporotic fracture, and a higher mortality rate after fracture among men compared with women. There are few approved therapies for osteoporosis in men. This observational study assesses the efficacy and safety of risedronate in the treatment of men with primary and secondary osteoporosis. A single-center, open label, randomized, prospective 1-year study was conducted in men with primary or secondary osteoporosis. Patients were randomized to risedronate (risedronate 5 mg/day plus calcium 1,000 mg/day and vitamin D 800 IU/day) or control groups (alfacalcidol 1 μg/day plus calcium 500 mg/day or vitamin D 1,000 IU/day plus calcium 800 mg/day). Bone mineral density (BMD) measurements, X-rays of the spine, a medical history and physical exam, and patient self-assessments of back pain were performed at baseline and 12 months. Blinded semi-quantitative fracture assessment was conducted by a radiologist. A total of 316 men with osteoporosis were enrolled in the trial (risedronate, n=158; control, n=158). At 1 year lumbar spine BMD increased by 4.7% in the risedronate group versus an increase of 1.0% in the control group (P<0.001). Significant increases in BMD at the total hip and femoral neck were also observed with risedronate compared with the control group. The incidence of new vertebral fracture in the risedronate group was reduced by 60% versus the control group (P=0.028). Daily treatment with risedronate for 12 months significantly increased BMD at the lumbar spine, femoral neck and total hip and significantly reduced the incidence of new vertebral fractures. This is the first prospective, randomized, controlled trial to demonstrate a significant reduction in vertebral fractures in 1 year in men with primary or secondary osteoporosis.     

Alendronate treatment for hip osteoarthritis: prospective randomized 2-year trial

We examined the clinical efficacy of alendronate treatment for hip osteoarthritis using multiple outcome measures. Fifty patients with symptomatic hip osteoarthritis were enrolled in this prospective trial. The patients were randomly assigned to an alendronate group (35 mg/week alendronate and 600 mg/day calcium lactate) or a control group (600 mg/day calcium lactate) for 2 years. The groups were compared with regard to the following five parameters. The primary outcome measures are the following: (1) the Western Ontario and McMaster Universities (WOMAC) osteoarthritis pain score and the visual analog score (VAS). The secondary outcome measures are the following: (2) joint space width (JSW) measured on radiographs using a semiautomatic computer software, (3) the biochemical markers urinary N-telopeptide of type I collagen (NTX-I) and C-terminal cross-linking telopeptide of type II collagen (CTX-II), (4) dual-energy X-ray absorptiometry of the hip and lumbar spine, and (5) bone marrow edema on magnetic resonance images. The alendronate group showed pain improvement trends in VAS and WOMAC scores, whereas the control group showed worsening of pain. The alendronate group showed significant improvement in WOMAC pain scores after 12 months (p?=?0.031) but no significant prevention of structural osteoarthritis progression, defined as a decrease in JSW >0.30 mm or conversion to total hip arthroplasty. There was significantly larger decrease in the biochemical markers and significantly increased bone density in the alendronate group. Alendronate treatment by standard dose for osteoporosis showed clinical efficacy for decreasing pain but failed to show preventive effects for structural progression of hip osteoarthritis.     

Alfacalcidol in men with osteoporosis: a prospective, observational, 2-year trial on 214 patients

Due to pleiotropic-synergistic actions on bone, muscle, gut, brain and different other non-skeletal tissues, alfacalcidol is an interesting drug for treating osteoporosis. In studies on glucocorticoid-induced osteoporosis, men have always been treated with calcitriol or this active D-hormone prodrug, but there is no study of male patients only in the literature. The AIM-Trial (Alfacalcidol In Men) is an extension of the control group (n = 158) of our former risedronate study in male osteoporosis (Ringe et al. in Rheumatol Int 29:311–315, 2009). In that study, we treated daily those controls with prevalent vertebral fractures with 1 μg alfacalcidol + 500 mg calcium (group A) and those without prevalent vertebral fractures with 1,000 IU plain vitamin D (Vit. D) + 1,000 mg calcium (group B). Subsequently, we added an additional 56 pairs of patients to these two groups: 28 with and 28 without prevalent vertebral fractures, reaching a total of 214 cases. That means with this design, we are comparing two groups with a different risk at onset. Due to the prevalent vertebral fractures and lower average bone mineral density (BMD) values, there was a higher risk of incident fractures in group A. After 2 years, we found significantly higher increases in lumbar spine BMD (+3.2 vs. +0.8 %) and total hip BMD (+1.9 vs. ?0.9 %) in group A and B, respectively. Eighteen incident falls were recorded in the alfacalcidol group and 38 in the group treated with Vit. D (p = 0.041). There were significantly lower rates of patients with new vertebral and non-vertebral fractures in group A than in group B. Back pain was significantly reduced only with alfacalcidol. Concerning the incidence of new non-vertebral fractures, we found that there was a relation to renal function in the two groups. The advantage for alfacalcidol was mainly due to a higher non-vertebral fracture-reducing potency in patients with a creatinine clearance (CrCl) below 60 ml/min (p = 0.0019). There were no serious adverse events (SAE), and the numbers of mild-to-moderate adverse events (AE) were not different between groups. Despite the higher initial fracture risk in the alfacalcidol group, 2-year treatment with this active D-hormone prodrug showed a higher therapeutic efficacy in terms of BMD, falls and fractures. One important advantage of alfacalcidol may be that it is effective even in patients with mild-to-moderate renal insufficiency.     

阿伦膦酸钠防治原发性骨质疏松症

目的观察阿伦膦酸钠（福善美Ｆｏｓａｍａｘ）对原发性骨质疏松症妇女治疗的有效性和安全性。方法本研究为多中心开放研究，８１例原发性骨质疏松症妇女接受每日口服福善美１０ｍｇ和元素钙５００ｍｇ（碳酸钙）。平均年龄６５±６岁，绝经年限１５±６年，完成３月、６月和１２月治疗者分别有７９、７６和７０例。观察用药后骨密度的改变及不良反应。结果腰椎２４（Ｌ２４）骨密度于治疗３月、６月和１２月时均较疗前有非常明显的升高（Ｐ＜０．００１），升高率分别为２．８％、４．１％和６．３％。服药６月较３月、１２月较６月均见进一步增高（Ｐ＜０．０１）。髋部三个部位的骨密度在３月、６月和１２月都较疗前有显著升高，其中以大转子最显著（Ｐ＜０．００１），升高２．６％～２．９％，其次为股骨颈和Ｗａｒｄｓ三角，均较疗前有增高，但在１２月治疗期间未见逐步进行性增高。与试验药物很可能有关的不良反应有４例，主要为上消化道症状。未发生与药物有关的严重不良反应。结论福善美对中国妇女骨质疏松症治疗一年表明其是有效和安全的。     

Alendronate treatment for osteoporosis: a review of the evidence

Alendronate, a bisphosphonate indicated for the management of osteoporosis, is an antiresorptive agent that directly inhibits osteoclast activity. It reduces bone turnover and increases spine and hip BMD. Equivalent effects on turnover and BMD have been reported with once-weekly dosing, using seven times the daily dose. Among 3658 women with osteoporosis enrolled in the Fracture Intervention Trial (FIT), there was a 53% reduction in hip fractures, a 48% reduction in morphometric vertebral fractures, a 45% reduction in clinical vertebral fractures, and a 30% reduction in all clinical fractures. Each of these differences was already statistically significant within 12 months of starting treatment. The drug is safe and well tolerated.     

Extensive aetiological investigations in acute pancreatitis: results of a 1-year prospective study.

BACKGROUND: Epidemiological data on acute pancreatitis are poorly defined. AIMS: To prospectively evaluate the aetiology of acute pancreatitis and to assess the benefits of intensive investigations. METHODS: In a prospective, 1-year study all cases of acute pancreatitis in the Nice catchment area were enrolled. Subjects underwent routine (serum calcium, phosphate and triglycerides; abdominal ultrasonography and CT scan) and additional, delayed intensive investigations (ERCP with bile sampling and/or endoscopy ultrasonography). RESULTS: One hundred and twenty-one cases were included. After routine investigations, a biliary, alcoholic, miscellaneous or unknown origin was diagnosed in 43%, 31.4%, 9.9% and 15.7%, respectively. In subjects with biliary pancreatitis, 43% had no previous history of biliary disease. In the alcohol-related subgroup, pancreatitis recurred in 18.5% during 114.5 days mean follow-up. In subjects with a first episode of alcoholic pancreatitis, delayed supplemental investigations revealed underlying chronic pancreatitis in 92.8%. After routine investigations, a diagnosis of pancreatitis of unknown origin was made in 15.7% (n = 19) of subjects. Additional investigations revealed an underlying cause in 57.8% of these patients (n = 11), including malignancy (n = 3) and biliary disease (n = 4), reducing the overall rate of pancreatitis with no apparent cause to 6.6%. CONCLUSIONS: Investigative techniques, particularly ERCP, will reveal the underlying aetiology of pancreatitis in the majority of patients presenting with 'idiopathic' pancreatitis and should be considered when routine tests are negative.     

Effects of intensified antihypertensive treatment in diabetic nephropathy: mortality and morbidity results of a prospective controlled 10-year study.

OBJECTIVE: The aim of this study was to describe the effect of intensified antihypertensive therapy based on a structured teaching and treatment programme on the prognosis of hypertensive type 1 (insulin-dependent) diabetic patients with kidney disease. DESIGN: The study was a controlled, prospective, parallel, 10-year follow-up trial. PATIENTS AND INTERVENTIONS: A sequential sample of 91 hypertensive type 1 diabetic patients with overt diabetic nephropathy was prospectively followed for 10 years. Forty-five patients (intensified antihypertensive therapy; IT group) participated in an intensified antihypertensive therapy programme and 46 patients received routine antihypertensive treatment as provided by family physicians, consultants and local hospitals (routine antihypertensive therapy; RT group). OUTCOME MEASURES: The main endpoint was death; secondary endpoints were renal replacement therapy, blindness and amputation. RESULTS: Blood pressure was reduced in the IT group and increased in the RT group. During the follow-up period, 29 patients died, seven in the IT group and 22 in the RT group. The survival curves were significantly different (P = 0.0008). The main causes of death were cardiac. In a multiple Cox proportional hazards model, allocation to the IT group reduced the mortality risk [relative risk (RR) = 0.213; 95% confidence interval 0.089-0.509, P = 0.00051, while age (P = 0.0039) and mean blood pressure (P= 0.0113) increased this risk. In multiple Cox or multiple logistic regression models, the risks of dialysis (RR = 0.269, 95% confidence interval 0.110-0.656, P = 0.0039), blindness (odds ratio = 0.158, 95% confidence interval 0.037-0.684, P= 0.0136), and amputation (RR = 0.181, 95% confidence interval 0.047-0.703, P= 0.0135) were significantly lower in the IT group compared with the RT group (log rank P = 0.0008). CONCLUSION: We conclude that intensified antihypertensive treatment, based on a hypertension teaching and treatment programme, reduces long-term morbidity and mortality in patients with diabetic nephropathy.     

Psychological personality traits and development of cardiovascular diseases in young men (results of a 10-year prospective study

Cardiovascular abnormalities developed in 7.3% among physically and mentally healthy males aged 20-29 years after 10 years of practical activities that made it necessary to take crucial decisions under conditions of time shortage and information gap, to show determination and courage. The incidence rate for cardiovascular diseases was 38.8% among males with asthenic personality traits and 6.9% in those with sthenic traits (p less than 0.001). In persons with well-balanced personality traits, cardiovascular diseases were ascertained not to develop. The disparity between the psychological traits and those demanded by occupational activities is the major pathogenic factor as considered by the authors.     

Protection from rotavirus reinfection: 2-year prospective study.

To measure protection induced by natural rotavirus infection, 163 infants enrolled in a rotavirus vaccine trial were prospectively followed for 2 years. Serotype 1 rotaviruses were the predominant circulating strains during the study. Over the 2 years of observation, significantly fewer infants infected before enrollment developed a symptomatic reinfection (0 of 21) or any reinfection (4 of 21) compared with previously uninfected infants (P = .0003). Of the 60 infants who developed a primary rotavirus infection in the first year (40 symptomatic, 20 asymptomatic) only 4 were reinfected in the second year compared with 29 of 82 subjects not previously infected (P = .00003). Asymptomatic primary infection appeared to be as protective as symptomatic primary infection. The only symptomatic reinfections occurred in 2 subjects who did not develop rotavirus antibody after the initial detection of rotavirus. An age-related reduction in the ratio of symptomatic to asymptomatic primary rotavirus infection was also detected. In this study, protection against homotypic serotype 1 reinfection appeared to last greater than or equal to 2 years.     

Predicting the onset of knee pain: results from a 2-year prospective study of new workers

OBJECTIVE: To determine the relative contribution of work-related mechanical (injury) factors and psychosocial factors to the onset of a new episode of knee pain, in a cohort of newly employed workers. METHODS: A prospective cohort study of newly employed workers from 12 diverse occupational settings in England (The New Workers Study). 859 newly employed workers, free of knee pain, were identified. Information about occupational mechanical factors (manual handling and postural activities), the occupational physical environment, and psychological and psychosocial factors was collected by self-completion questionnaires. Participants were followed up after 12 and 24 months to identify cases of knee pain onset. Generalised estimating equations were used to estimate the risk of new-onset knee pain, with respect to the exposures previously measured. RESULTS: In total, over the 2-year follow-up period, 108 cases of new-onset knee pain were observed. Mechanical load, postural factors, psychological distress and work-place psychosocial factors all influenced the risk of new-onset knee pain over the 2-year follow-up period. On multivariate analysis, two factors remained independently predictive of knee pain onset: lifting or carrying heavy weights in one hand, and the level of general psychological distress. CONCLUSION: In addition to mechanical (injury) factors, psychological factors are important risk factors for knee pain onset as shown in a population of young newly employed workers.     

Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results from the DIVA study

OBJECTIVE: An effective and well tolerated intravenous (IV) bisphosphonate could provide a new treatment method for patients with osteoporosis. The Dosing IntraVenous Administration (DIVA) study was designed to identify the optimal ibandronate IV injection schedule for the treatment of postmenopausal osteoporosis by comparing the efficacy and tolerability of 2- and 3-monthly injections with the previously evaluated daily oral ibandronate regimen. We report the effects on lumbar spine and proximal femur bone mineral density (BMD) and bone resorption markers over 2 years. METHODS: This randomized, double-blind, double-dummy, noninferiority study recruited 1395 women (aged 55-80 yrs; > or = 5 yrs since menopause) with osteoporosis [mean lumbar spine (L2-L4) BMD T-score < -2.5 and > or = -5.0]. Patients received IV ibandronate (2 mg every 2 mo or 3 mg every 3 mo) plus daily oral placebo, or 2.5 mg daily oral ibandronate plus 2- or 3-monthly IV placebo. Supplemental vitamin D (400 IU) and calcium (500 mg) were provided throughout the 2-year study. RESULTS: At 2 years, the 2- and 3-monthly IV regimens achieved statistically noninferior and also superior increases in lumbar spine BMD compared with the daily regimen (6.4% and 6.3% vs 4.8%, respectively; p < 0.001). Greater increases were also obtained with IV ibandronate versus daily in proximal femur BMD. Serum concentrations of the biochemical marker of bone resorption C-telopeptide of the alpha-chain of type I collagen were reduced to a similar extent in all treatment arms (53.4%-59.9%). The tolerability profile of the IV regimens was similar to that observed with daily oral therapy. CONCLUSION: Ibandronate IV injections are an effective and well tolerated treatment for postmenopausal osteoporosis and provide a useful alternative to oral dosing.