老年性骨质疏松性骨折的发生与预防

骨质疏松性骨折是一项在老年人中极为常见和严重的健康问题。随着人口的老龄化,骨量丢失在变成一个日益严重的临床问题。然而老年人骨量丢失这个情况很少被人们发觉,因而不能得到很好的治疗。除了骨矿物含量密度(骨密度)的下降,导致骨质疏松性骨折的因素常与影响姿势稳定性的神经肌肉失调有关。骨质疏松性骨折的预防围绕充足的矿物营养,包括每日钙和维生素D的供应以及抗骨吸收药物的应用,两者都可以降低骨折发生风险。预防骨折还需要预防跌倒,并减少跌倒产生的冲击力。因此,药物和非药物干预同样重要。本综述也探讨了骨折风险预测工具(FRAX)的使用,它可以通过使用患者的特定数据来预测特定时间内骨折的风险。当前,老年性骨质疏松症仍缺乏诊断和治疗,但年龄并不能成为骨质疏松性骨折干预的障碍。     

Characteristics of elderly patients admitted to an urban tertiary care hospital with osteoporotic fractures: correlations with risk factors, fracture type, gender and ethnicity

Osteoporosis is a major public health problem in the United States of America and around the world, largely due to the morbidity and mortality associated with osteoporotic fractures. In the past decade, large epidemiologic studies have contributed greatly to our understanding of patients who fracture. However, most studies are limited to postmenopausal white women. In this retrospective review, we analyze data from 185 men and women with acute fragility fractures who received osteoporosis consultations during admission to a single urban hospital between 2001 and 2003. Men and women differed in terms of risk factors for falls and osteoporosis but had areal bone mineral density (BMD) measurements remarkably similar, except at the total hip. Black and Hispanic subjects with fractures were significantly younger than whites yet were much more likely to have serious co-morbidities, such as diabetes mellitus and hypertension. In spite of significantly higher BMD measurements, black patients had the highest rates of vitamin D deficiency and secondary hyperparathyroidism. Patients admitted with hip fractures differed from those with non-hip fractures on a number of important variables. Based on these data, we conclude that elderly subjects admitted to an urban hospital with osteoporotic fractures are a heterogeneous group, with features that vary according to fracture type, gender and ethnicity. Future studies of patients with clinical fragility fractures should include ample numbers of men and ethnic minorities, since differences in underlying risk factors may suggest alternative strategies for fracture prevention.     

Current osteoporosis treatment: reasons for adding vitamin D to alendronate

Recently, many studies showed need to administer vitamin D in treatment of osteoporosis. Vitamin D deficiency was proved in postmenopausal women with osteoporosis. Effects of vitamin D resulted in lower risk of fractures and falls, as well as improvement of neuromuscular performances. In more than ten years of practice and several short- and long-term clinical studies alendronate lowered the risk of vertebral and extravertebral fractures, improved BMD of all measured sites in postmenopausal women and men with osteoporosis. Positive results of alendronate were demonstrated in different entities like persons of various ages and grades of lower BMD or patients with glucocorticoid-induced osteoporosis. Combination of vitamin D with efficacious antiresorptive drug alendronate maintains all pharmacological features and proves clinical effects of lx weekly alendronate, partly eliminating need for vitamin D supplementation.     

Optimal Use of Vitamin D When Treating Osteoporosis

Inadequate serum 25-hydroxyvitamin D (25[OH]D) concentrations are associated with muscle weakness, decreased physical performance, and increased propensity in falls and fractures. This paper discusses several aspects with regard to vitamin D status and supplementation when treating patients with osteoporosis in relation to risks and prevention of falls and fractures. Based on evidence from literature, adequate supplementation with at least 700 IU of vitamin D, preferably cholecalciferol, is required for improving physical function and prevention of falls and fractures. Additional calcium supplementation may be considered when dietary calcium intake is below 700 mg/day. For optimal bone mineral density response in patients treated with antiresorptive or anabolic therapy, adequate vitamin D and calcium supplementation is also necessary. Monitoring of 25(OH)D levels during follow-up and adjustment of vitamin D supplementation should be considered to reach and maintain adequate serum 25(OH)D levels of at least 50 nmol/L, preferably greater than 75 nmol/L in all patients.     

Management of osteoporosis in geriatric populations

The incidence of osteoporotic fractures increases with advancing age and is associated with significant health care expenditures, particularly related to hip fractures and loss of quality of life. Unfortunately, few studies have included subjects 80 years of age and older to help guide management of elderly patients who are living in the community or in long-term care facilities. Treating this age group encompasses the same general measures and pharmacologic therapies as in younger adults. Focusing on fall prevention and adequate vitamin D is essential. All prevention strategies in the elderly for fracture risk reduction should include simple vitamin D and calcium supplementation. However, for those at high risk of fracture, adding pharmacologic therapy should be considered. This article reviews recent research findings of general measures and pharmacologic therapy that are applicable to managing osteoporosis in the elderly.     

Hypovitaminosis D in patients with osteoporotic hip fractures

BackgroundInadequate serum vitamin D levels are associated with secondary hyperparathyroidism, increased bone turnover, bone loss and increased fracture risk. Vitamin D is well recognized to be suboptimal in older patients when compared to age-matched controls. There are no published studies on the prevalence of hypovitaminosis D in Indian population with fragility fractures around the hip associated with osteoporosis and comminution at the fracture site.AimTo investigate the prevalence of hypovitaminosis D in patients admitted with osteoporotic hip fractures and associated fracture site comminution in a South Indian Institute.Material & MethodsA prospective cross sectional study was conducted on 100 patients admitted with osteoporotic hip fracture. Measurement of serum 25-hydroxy vitamin D was done and the same was correlated with the degree of osteoporosis using Singh’s index and fracture site comminution.ResultsOut of 100 patients studied, 92% had hypovitaminosis D with mean vitamin D level of 16.08 ± 5.95 ng/dl (65% vitamin D deficiency with mean 13.16 ± 4.24 ng/dl and 27% vitamin D insufficiency with mean 23.11 ± 2.62 ng/dl) and 94% had osteoporosis with Singh’s index grade 3 or less. Out of the 36 patients with fracture site comminution 34 patients (94%) had hypovitaminosis D and 33 patients (91.6%) had osteoporosis. Statistical significance was established for all the variables.ConclusionSignificant association was found between hypovitaminosis D, osteoporosis and fracture site comminution. High prevalence of hypovitaminosis D in patients presenting with hip fractures and fracture site comminution implicates the necessity for proper evaluation and effective supplementation of vitamin D in elderly patients along with anti-osteoporotic regimens for effective prevention and appropriate management of osteoporotic hip fractures.     

Ertapenem-associated neurotoxicity in the spinal cord injury (SCI) population: A case series

Objectives: The primary objective was to review the literature regarding methodologies to assess fracture risk, to prevent and treat osteoporosis and to manage osteoporotic fractures in SCI/D.

Study Design: Scoping review.

Settings/Participants: Human adult subjects with a SCI/D.

Outcome measures: Strategies to identify persons with SCI/D at risk for osteoporotic fractures, nonpharmacological and pharmacological therapies for osteoporosis and management of appendicular fractures.

Results: 226 articles were included in the scoping review. Risk of osteoporotic fractures in SCI is predicted by a combination of DXA-defined low BMD plus clinical and demographic characteristics. Screening for secondary causes of osteoporosis, in particular hyperparathyroidism, hyperthyroidism, vitamin D insufficiency and hypogonadism, should be considered. Current antiresorptive therapies for treatment of osteoporosis have limited efficacy. Use of surgery to treat fractures has increased and outcomes are good and comparable to conservative treatment in most cases. A common adverse event following fracture was delayed healing.

Conclusions: Most of the research in this area is limited by small sample sizes, weak study designs, and significant variation in populations studied. Future research needs to address cohort definition and study design issues.     

住院骨质疏松性骨折患者危险因素与干预措施

目的 探讨住院老年骨质疏松骨折发生的危险因素,为指导骨质疏松性骨折的预防提出干预措施。方法 选择2010年5月～2012年 5 月在我院住院的203例老年骨质疏松症患者为研究对象,根据患者是否出现骨折分为老年骨质疏松性骨折组和老年骨质疏松症无骨折组,采用自编问卷的方法收集符合条件的患者的临床资料。采用多因素 Logistic回归分析骨质疏松性骨折患者的危险因素。结果 骨密度是骨质疏松症并发骨折的保护因素,而年龄、低钙饮食、跌倒、脆性骨折史及骨折家族史是发生老年骨质疏松性骨折的危险因素。结论 老年骨质疏松症并发骨折受多种因素影响,可从饮食、体育锻炼及药物等多方面进行干预。     

Nonpharmacological prevention of osteoporotic fractures

In postmenopausal women, the nonpharmacological prevention of osteoporotic fractures pursues the dual objective of minimizing bone loss and preventing falls. In women with a low fracture risk, optimizing the dietary intake of calcium is the main nutritional goal. Regular sustained physical activity should be encouraged. In older women, the high risk of proximal femoral fractures warrants a number of preventive measures, including calcium and vitamin D supplementation, correction of protein deficiency if needed, and minimization of the risk of falls. Hip protectors may be useful in institutionalized women at high risk for falls. These nonpharmacological measures should be part of a comprehensive customized management program used to complement standard pharmacological therapy.     

Is there a differential response to alfacalcidol and vitamin D in the treatment of osteoporosis?

There is a decline in serum 25 hydroxyvitamin D (25OHD), 1,25 dihydroxyvitamin D (1,25(OH)₂D), and calcium absorption with advancing age, which may lead to secondary hyperparathyroidism and bone loss. Studies show a relationship between serum 25OHD and bone density in older men and women, with an inverse correlation between bone density and parathyroid hormone (PTH). Vitamin D supplementation in this age group improves calcium absorption, suppresses PTH, and decreases bone loss. Vitamin D many also reduce the incidence of hip and other nonvertebral fractures, particularly in the frail elderly who are likely to have vitamin D deficiency. Patients with established vertebral osteoporosis have lower calcium absorption than age-matched control subjects, possibly due to reduced serum 1,25(OH)₂D or to relative resistance to the action of vitamin D on the bowel. Malabsorption of calcium in women with vertebral crush fractures does not usually respond to treatment with physiological doses of vitamin D, but can be corrected by pharmacological doses of vitamin D or by low doses of calcitriol or alfacalcidol. In a recent randomized, controlled study in 46 elderly women with radiological evidence of vertebral osteoporosis, alfacalcidol 0.25 μg twice daily improved calcium absorption, decreased serum PTH, and reduced alkaline phosphatase, whereas vitamin D₂ 500–1000 IU daily had no effect over the 6-month study period. Studies of the effect of the vitamin D metabolites in the management of elderly women with established vertebral osteoporosis have yielded conflicting results, but suggest that alfacalcidol and calcitriol may decrease spinal bone loss and reduce the incidence of vertebral fractures. Although vitamin D supplementation decreases bone loss and fracture risk in the frail elderly, vitamin D metabolites may prove more useful in the treatment of elderly women with vertebral osteoporosis.     

The need for clinical guidance in the use of calcium and vitamin D in the management of osteoporosis: a consensus report

A European Union (EU) directive on vitamins and minerals used as ingredients of food supplements with a nutritional or physiological effect (2002/46/EC) was introduced in 2003. Its implications for the use of oral supplements of calcium and vitamin D in the prevention and treatment of osteoporosis were discussed at a meeting organized with the help of the World Health Organization (WHO) Collaborating Center for Public Health Aspects of Rheumatic Diseases (Liège, Belgium) and the support of the WHO Collaborating Center for Osteoporosis Prevention (Geneva, Switzerland). The following issues were addressed: Is osteoporosis a physiological or a medical condition? What is the evidence for the efficacy of calcium and vitamin D in the management of postmenopausal osteoporosis? What are the risks of self-management by patients in osteoporosis? From their discussions, the panel concluded that: (1) osteoporosis is a disease that requires continuing medical attention to ensure optimal therapeutic benefits; (2) when given in appropriate doses, calcium and vitamin D have been shown to be pharmacologically active (particularly in patients with dietary deficiencies), safe, and effective for the prevention and treatment of osteoporotic fractures; (3) calcium and vitamin D are an essential, but not sufficient, component of an integrated management strategy for the prevention and treatment of osteoporosis in patients with dietary insufficiencies, although maximal benefit in terms of fracture prevention requires the addition of antiresorptive therapy; (4) calcium and vitamin D are a cost-effective medication in the prevention and treatment of osteoporosis; (5) it is apparent that awareness of the efficacy of calcium and vitamin D in osteoporosis is still low and further work needs to be done to increase awareness among physicians, patients, and women at risk; and (6) in order that calcium and vitamin D continues to be manufactured to Good Manufacturing Practice standards and physicians and other health care professionals continue to provide guidance for the optimal use of these agents, they should continue to be classified as medicinal products.     

High prevalence of vitamin D deficiency and reduced bone mass in elderly women with Alzheimer’s disease

Patients with Alzheimer’s disease (AD) are at increased risk for falls and hip fractures. To better understand causes and prevention, we measured bone mineral density (BMD) in the second metacarpals of 46 ambulatory elderly women with AD and analyzed its relation to serum biochemical indices, sunlight exposure, and vitamin D intake. BMD was significantly less than in age-matched controls. In 26% of AD patients, the serum 25-hydroxyvitamin D (25-OHD) concentration was at a deficient level (5–10 ng/mL), and in 54% it was at an osteomalacic level (<5 ng/mL). Concentrations of ionized calcium were significantly lower in patients. Conversely, concentrations of serum bone Gla-protein and urinary hydroxyproline in patients were significantly higher than in controls. BMD correlated positively with 25-OHD concentration (p = 0.0041) and negatively with parathyroid hormone (PTH) concentration (p = 0.0022). PTH was higher in patients than in controls, and correlated negatively with 25-OHD (p < 0.0001). Many AD patients were sunlight-deprived and consumed less than 100 IU of vitamin D per day. We concluded that vitamin D deficiency due to sunlight deprivation and malnutrition, together with compensatory hyperparathyroidism, contributes significantly to reduced BMD in AD patients. Low BMD increases risk of hip fractures in patients with AD, but may be improved by vitamin D supplementation.     

骨质疏松性骨折防治新概念:补充韧骨元素镁、锌、铜、猛

常规补充钙和维生素D可防治骨质疏松,进一步减少骨质疏松性骨折发病率。骨强度由骨密度和骨质量决定,骨密度由高度矿化的无机盐（钙、磷、镁等）组成,骨质量主要由有机骨基质胶原纤维组成,而胶原蛋白合成必需有微量元素参加,特别是铜、锰和锌。本文主要介绍镁、锌、铜、锰对骨质 疏松症和骨质疏松性骨折防治的作用和临床研究,提出骨质疏松性骨折防治的新概念：补充韧骨元素镁、锌、铜、锰。     

Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women.

Long-term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short-term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [+/-SD] age, 74 +/- 1 years) with a 25-hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1-year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% ( p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1-year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women.     

Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study.

A 3-year prospective, randomized, placebo-controlled trial of oral clodronate 800 mg showed that the incidence of clinical fractures was decreased by 20% in 5596 elderly women unselected for osteoporosis. The effect occurred in the absence of systematic calcium and vitamin D supplementation and was observed across a wide range of BMDs. INTRODUCTION: To date, most studies with bisphosphonates have reported on their use in individuals selected to be at high risk for fracture usually by the presence of low BMD or a prior fragility fracture, usually of the spine. We wished to determine the effect of the bisphosphonate, clodronate, on the rate of fractures in women > or =75 years of age living in the community. MATERIALS AND METHODS: Women > or =75 years of age living in the general community in South Yorkshire and North Derbyshire, identified from general practice registers, were recruited by letter of invitation to a randomized, double-blind, controlled trial of 800 mg oral clodronate (Bonefos) or matching placebo daily over 3 years. The main outcomes were the incidences of hip and any clinical fracture. RESULTS: Of the 5579 elderly women included in the intention-to-treat analysis of efficacy, 114 had a new hip fracture during the 3-year treatment phase: 56 (2.0%) women in the clodronate group and 58 (2.1%) women in the placebo group (hazard ration [HR], 1.02; 95% CI, 0.71-1.47). Clodronate did, however, decrease the incidence of any clinical fracture by 20% (264 women [9.5%] versus 337 [12.1%] in the placebo group; HR, 0.80; 95% CI, 0.68-0.94). The incidence of osteoporosis-associated nonhip fractures was also significantly decreased by 29% (5.2% versus 7.4%; HR, 0.71; 95% CI, 0.57-0.87). The ability of clodronate to reduce the risk of osteoporotic fracture was independent of baseline BMD, but the number needed-to-treat was lower in the presence of osteoporosis. CONCLUSIONS: Oral daily clodronate can prevent fractures without significant adverse effects in elderly women living in the general community. The effect on hip fracture risk is not significant, but an effect similar to that at other nonvertebral sites cannot be excluded. This study suggests that antiresorptive therapies can reduce fracture incidence in high-risk individuals even in the presence of a normal or osteopenic BMD.     

Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease

A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer's disease (AD), who are prone to falls and may have osteoporosis. We previously showed deficiency of vitamins D and K1 causes reduced bone mineral density (BMD) in female AD patients. The present study was undertaken to address the possibility that treatment with vitamin K2 (menatetrenone; MK-4) may maintain BMD and reduce the incidence of nonvertebral fractures in elderly female patients with AD. In a random and prospective study of AD patients, 100 patients received 45 mg menatetrenone, 1000 IU ergocalciferol and 600 mg calcium daily for 2 years, and the remaining 100 (untreated group) did not. At baseline, patients of both groups showed vitamin D and K1 deficiencies. They also had high serum levels of parathyroid hormone (PTH) and Glu osteocalcin (OC) and low serum ionized calcium, indicating that vitamin D deficiency stimulates compensatory PTH secretion. During the 2-year study period, BMD in the second metacarpals increased by 2.3% in the treated group and decreased by 5.2% in the untreated group (P < 0.0001). Serum levels of vitamin K2 and 25-hydroxyvitamin D increased by 284.9% and 147.9%, respectively, in the treated group. Correspondingly, a significant decrease in Glu OC and PTH were observed, in association with an increased calcium levels, in the treated group. Twenty-two patients in the untreated group sustained nonvertebral fractures (15 with hip fractures, two fractures each at the distal forearm and the proximal femur, each one fracture at the proximal humerus, ribs, and pelvis), and three fractures (2 with hip fractures, one fracture at the proximal femur) occurred among the treated patients (P = 0.0003; odds ratio = 7.5). Treatment with MK-4 and vitamin D2 with calcium supplements increases the BMD in elderly female patients with AD and leads to the prevention of nonvertebral fractures.     

Bone mineral density in lung-transplant recipients before and after graft: prevention of lumbar spine post-transplantation-accelerated bone loss by pamidronate.

BACKGROUND: Lung-transplant recipients are at risk of osteoporosis. They may have low bone mass even before posttransplantation immunosuppressive therapy. We studied bone mineral density (BMD) before and after lung transplantation and compared the efficacy of antiresorptive therapies to calcium and vitamin D supplementation. METHODS: Areal BMD was assessed in 42 patients awaiting lung transplantation and measured again after surgery at 6 (n = 29), and at 12 months (n = 20). Nineteen patients received antiresorptive therapy (30 mg pamidronate IV every 3 months (n = 14), or hormonal replacement therapy (n = 5)), and 10 patients received only calcium and vitamin D supplements.RESULTS: Mean age- and gender-adjusted lumbar spine (LS) and femoral neck (FN) BMD was significantly decreased prior to transplantation (- 0.6 +/- 0.2, p< 0.01, and - 1.5 +/- 0.2 standard deviation, p < 0.001, respectively). At that time, 29% were osteoporotic (T-score < - 2.5 below the peak bone mass), while 55% were below - 1.0 T-score. Antiresorptive therapy decreased the rate of LS bone loss during the first 6 months and led to a significant increase of BMD at 1 year, with LS changes of + 0.2 +/- 0.1 vs - 0.4 +/- 0.1 Z-score in the calcium-vitamin D group (p< 0.002), and + 0.2 +/- 0.1 vs - 0.04 +/- 0.1 for FN (NS). One out of 20 patients experienced clinically evident fractures during antiresorptive therapy, and 3 out of 12 in the calcium-vitamin D group. CONCLUSION: A significant proportion of patients awaiting lung transplantation was osteoporotic or osteopenic. Antiresorptive therapy (pamidronate or hormone-replacement therapy (HRT)) prevented accelerated LS bone loss after graft.     

Amelioration of osteoporosis and hypovitaminosis D by sunlight exposure in hospitalized, elderly women with Alzheimer's disease: a randomized controlled trial.

In a random and prospective study, Alzheimer's disease (AD) patients were assigned to regular sunlight exposure (n = 132) or sunlight deprivation (n = 132) and followed for 1 year. Serum 25-OHD level increased by 2.2-fold in the sunlight-exposed group. Eleven patients sustained fractures in the sunlight-deprived group, and three fractures occurred among the sunlight-exposed group (p = 0.0362; odds ratio = 3.7). INTRODUCTION: A high incidence of fractures, particularly of the hip, represents an important problem in patients with Alzheimer's disease (AD), who are prone to falls and have osteoporosis. We previously showed that 25-hydroxyvitamin D (25-OHD) deficiency caused by sunlight deprivation with compensatory hyperparathyroidism causes reduced BMD in elderly women with AD. This study was undertaken to address the possibility that sunlight exposure with calcium supplementation may maintain BMD and reduce the incidence of nonvertebral fractures in elderly women with AD. MATERIALS AND METHODS: In a random and prospective study, AD patients were assigned to regular sunlight exposure (n = 132) or sunlight deprivation (n = 132) and followed for 1 year. BMD of the second metacarpal bone was measured using a computed X-ray densitometer (CXD). The CXD method measures BMD and cortical thickness at the middle of the second metacarpal bone on a radiogram of the hand and an aluminum step wedge as a standard (20 steps; 1 mm/step). Incidence of nonvertebral fractures in the two patient groups during the 1-year follow-up period was assessed. RESULTS AND CONCLUSION: At baseline, average hospitalization period was 1.7 years in both groups, and activity of daily living (ADL) was decreased. Patients of both groups showed vitamin D deficiency caused by sunlight deprivation and decreased dietary intake of vitamin D with compensatory hyperparathyroidism. The exposed group patients were exposed to sunlight (3615 minutes/year). BMD increased by 2.7% in the sunlight-exposed group and decreased by 5.6% in the sunlight-deprived group (p < 0.0001). Serum 25-OHD level increased from 24.0 to 52.2 nM in the sunlight-exposed group. Eleven patients sustained fractures in the sunlight-deprived group, and three fractures occurred among the sunlight-exposed group (p = 0.0362; odds ratio = 3.7). Sunlight exposure can increase the BMD of vitamin D-deficient bone by increasing 25-OHD concentration and lead to the prevention of nonvertebral fractures.     

Fracture incidence and characterization in patients on osteoporosis treatment: the ICARO study.

None of the available osteoporosis therapies have been shown to completely abolish the risk of fractures. In clinical practice, the outcome may be even poorer. In 880 patients prescribed with antiresorptives (alendronate, risedronate, and raloxifene) for >1 year, a fragility fracture was recorded in 8.9%/year of them. This incidence is considerably higher than that observed in randomized clinical trials, and it was significantly related to poor compliance and lack of supplementation with calcium and vitamin D. INTRODUCTION: Osteoporotic fracture is one of the most important public health concerns among the elderly. Currently available therapies have been shown to significantly decrease the risk of fracture, although none of them completely abolishes this risk. In clinical practice, poor treatment response may also result from a number of other factors. MATERIALS AND METHODS: The Incidence and ChAracterization of inadequate clinical Responders in Osteoporosis (ICARO) is a multicenter, observational study carried out in Italy. It aimed to analyze, in postmenopausal women with established osteoporosis, the risk factors for an "inadequate clinical response" to drug therapy, defined as the occurrence of new vertebral or nonvertebral fragility fractures in patients prescribed, for at least 1 year, alendronate, risedronate, or raloxifene, with a compliance >50%. RESULTS: In 880 patients treated with antiresorptive agents for a median of 2.0 years (95% CI: 1.0-4.5) years, the "inadequate clinical responder (ICR)" subjects over the observation period were 220 (25%), with an annual incidence of 8.9%. ICRs, compared with "adequate clinical responders (ACRs)," had more pretreatment fractures and were treated longer (2.8 versus 1.8 years; p < 0.001). After multiple adjustment for these confounding factors, significant determinants of inadequate clinical response were a poorer treatment compliance and a less frequent co-administration of calcium and vitamin D supplements. CONCLUSIONS: The incidence of fractures during treatment with antiresorptive agents in a clinical setting is considerably higher than that observed in randomized clinical trials. Inadequate compliance to treatment and lack of supplementation of calcium and vitamin D are major determinants of this poor response.