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Perception of osteoporosis by Belgian women who work in a university hospital.

Campaigns to increase 'awareness' of osteoporosis have been organized. The aim of this study was to assess how Belgian women who benefit from superior conditions favoring 'awareness' perceive osteoporosis as being an important disease. A survey sent to the private home of all the women working in a university hospital in Brussels (n = 1154). From a list of 13 diseases the women were asked to rank, by order of importance, the five which they found to be the most important for a woman of their age. They were also asked about visits to physicians, and screening procedures. The response rate was 55.4%. A high uptake of medical visits and screening procedures was reported: 89% of the women had seen a general practitioner or a gynecologist and 81.6% had undergone at least one gynecologic examination during the previous year. Three times more women had ever undergone mammography than a bone mineral density (BMD) measurement. Overall, 18.1% reported having had a BMD measurement in the past. In women over 50 years, 61% reported having had a BMD measurement and 92.7% having had a mammogram. Osteoporosis was ranked among the five most important diseases by 19.4% of women before the age of 50 years and by 39.3% after that age, far behind breast cancer (respectively 86.3% and 77.7%) and uterine cancer (respectively 74.2% and 58.0%). Thus even among a population of women who benefit from superior conditions for information and screening, the perception of osteoporosis remains low, as does the uptake of osteoporosis screening.

Absorptiometry, Photon↗

Site-specific variation in the classification of osteoporosis, and the diagnostic reclassification using the lowest individual lumbar vertebra T-score compared with the L1-L4 mean, in early postmenopausal women.

In this study we report first the concordance and variation in diagnostic osteoporosis classification using multiple skeletal site measurements compared with the lumbar spine only; and secondly, at the lumbar spine, the variation and diagnostic osteoporosis reclassification using the lowest individual vertebra T-score compared with the L1-L4 mean T-score. One hundred and fifty early postmenopausal women were evaluated as part of the recruitment for a multicenter osteoporosis prevention study. Bone mineral density (BMD) was restricted such that no more than 10% of the subjects had a lumbar spine BMD below 0.8 g/cm2. Forty-seven per cent of the subjects were classified as having low bone mass (T-score < or = -1.0) at the lumbar spine, 63% at the mid-forearm, 39% at the distal forearm and 50% at the hip (p < 0.05). The greatest proportion of subjects were categorized as osteoporotic at the lumbar spine, followed by the forearm and then the hip. Correlation between sites ranged from 0.57 to 0.60 (p < 0.01). Eighty-one percent of the subjects had a significant difference between their highest and lowest individual lumbar vertebra T-score (defined as a difference outside the 90% confidence interval coefficient of variation T-score value). Using the lowest individual lumbar T-score, recategorized 33% of the subjects classified as osteopenic (based on the mean L1-L4 T-score) as osteoporotic, and 23% of those classified as normal as osteopenic (p < 0.05). Of all four vertebrae, L2 had the highest T-score in 37.7% of the subjects (mean -0.3) and L4 the lowest in 61% (mean -1.5) (mean difference 1.2 units, 95% CI 0.7 to 1.7). The classification of osteoporosis varies according to skeletal site, with pronounced differences in the early menopausal population. T-scores are useful for characterizing subjects with the highest risk of osteoporosis but BMD and fracture risk must be recognized in a continuum. Individual T-scores of the lumbar vertebrae show wide variation in the absence of degenerative spinal disease or vertebral collapse and the use of the lowest, significantly different, individual lumbar vertebra T-score reclassified over half of the subjects in this study. This poses a great therapeutic dilemma in clinical practice, particularly if these fractures are at higher risk of future collapse.

Bone Density↗

Association of a G2014A transition in exon 8 of the estrogen receptor-alpha gene with postmenopausal osteoporosis.

We report the association of a newly identified synonymous G2014A single nucleotide polymorphism (SNP) which does not alter the amino acid sequence in exon 8 of the estrogen receptor-alpha (ERalpha) gene with osteoporosis in Thai postmenopausal women. Subjects consisted of 228 postmenopausal women aged more than 55 years divided into two groups--with vertebral or femoral osteoporosis (n = 106) or without osteoporosis (n = 122)--according to bone mineral density (BMD) criteria. The exon 8 G2014A SNP, which is 6 nucleotides upstream from the end of the stop codon, was identified by PCR-RFLP. Data are expressed as the mean and 95% CI. The allele frequency of the G2014A polymorphism was 26.4% in osteoporotic subjects and was significantly higher than that in non-osteoporotic women (15.2%) (p<0.05). By stepwise logistic regression analysis, it was found that the G2014A polymorphism was related to the presence of osteoporosis (odds ratio 2.7 per A allele, 95% CI 1.49-4.76) independently of body weight (odds ratio 0.93 per kg, 95% CI 0.89-0.96) and years since menopause (odds ratio 1.12 per year, 95% CI 1.08-1.19). In a multiple linear regression model, L2-L4 BMD of osteoporotic subjects was associated with body weight (p<0.05), endogenous estradiol levels (p<0.05) and the G2014A genotype (p<0.001), while it was related only to body weight (p<0.05) and estradiol levels in non-osteoporotic women (p<0.05). We conclude that a G2014A SNP in exon 8 of ERalpha is associated with the presence and severity of postmenopausal osteoporosis. Linkage disequilibrium between this polymorphism and the 3'-untranslated region of the ERalpha gene which may participate in the regulation of ERalpha gene expression remains to be determined.

Aged↗

Challenges for model-based economic evaluations of postmenopausal osteoporosis interventions.

Assessing the cost-effectiveness of long-term treatment for osteoporosis requires use of mathematical models to estimate health effects and costs for competing interventions. The primary motivations for model-based analyses include the lack of long-term clinical trial outcome data and the lack of data comparing all relevant treatments within randomized clinical trials. We report on specific modeling challenges that arose in the development of a model of the natural history of postmenopausal osteoporosis that is suitable for assessing the cost-effectiveness of osteoporosis interventions among various population subgroups in diverse countries. These include choice of modeling changes in bone mineral density (BMD) or in fracture rate, definition of health states, modeling mortality and costs of long-term care following fracture, incorporation of health utility, and model validation. This report should facilitate future postmenopausal osteoporosis model development and provide insight for decision-makers who must evaluate model-based economic analyses of postmenopausal osteoporosis interventions.

Aged↗

An osteoporosis clinical pathway for the medical management of patients with low-trauma fracture.

Patients with an osteoporotic fracture have at least a 2-fold risk for additional fracture and should benefit from targeted diagnostic and treatment procedures for osteoporosis. To address this issue, we set up an osteoporosis clinical pathway (OCP) for the medical management of patients with low-trauma fracture. Following acute management of the fracture by the orthopedic team, patients are enrolled in the pathway, which is based on an interaction between the OCP multidisciplinary team, orthopedic surgeons and/or primary care physicians. After collection of patient data, suggestions for additional diagnostic examinations with their interpretation, and treatment proposals are made. Patients and their families are also invited to attend a multidisciplinary interactive educational program on physical therapy, lifestyle habits and nutrition. During a 36-month period, 385 patients (311 women, 74 men; mean age +/- SD: 73.0 +/- 13.5 years; hip fracture 45%, ankle/tibia 24%, proximal humerus 8.6%, spine 5.5%, pelvis 3.9%, distal forearm 3.6%, other sites 17.4%) were enrolled in the OCP. An osteoporosis awareness questionnaire administered within 10 days of fracture showed that 73% of patients believed that their fracture was not related to the disease. Dual-energy X-ray absorptiometry, performed in 63% of patients, showed that 86% had low bone mass or osteoporosis. Specific antiosteoporotic therapy was proposed for 33% of patients in addition to calcium and vitamin D supplements, the latter suggested for 93%. A survey performed in 216 patients 6 months later, indicated that 63% of the suggested treatments had been prescribed and that 67% of this group were continuing treatment. Such a clinical pathway for the medical management of low-trauma fracture can help to identify patients with osteoporosis in a high-risk population, provide support to the orthopedic surgeon and/or the primary care physician for diagnostic and treatment procedures, and should significantly contribute to increase awareness of the disease in patients and their families.

Accidental Falls↗

Is distal forearm fracture in men due to osteoporosis?

Although widely regarded as a disease of women, osteoporosis does cause considerable morbidity and mortality in men. The lifetime risk of an osteoporortic fracture for a man is 1 in 12 and 30% of all hip fractures occur in men. In women, low-trauma distal forearm fracture is widely regarded as a typical early manifestation of postmenopausal osteoporosis. Traditionally, this has not been thought to be the case for men. We present a case-control study of 147 men with distal forearm fracture compared with 198 age-matched controls. The controls were selected from a pre-existing database of dual-energy X-ray absorptiometry scans of healthy volunteers. Both groups were sent questionnaires regarding basic demographics, fracture history and risk factors for osteoporosis, and the fracture group was asked to attend for bone densitometry. There were 103 responses from the fracture group (70%), of whom 67 (47%) underwent densitometry. There were 165 (83%) responses from the control group. Secondary causes of osteoporosis could be identified in 51% of the fracture group and 37% of the control group. The fracture group had significantly lower bone mineral density at all sites measured compared with the controls (0.75 g/cm(2) vs 0.85 g/cm(2) at the femoral neck, p<0.0001; 0.95 g/cm(2) vs 1.03 g/cm(2) at the total femur, p = 0.001; and 0.99 g/cm(2) vs 1.06 g/cm(2) at the lumbar spine, p = 0.001). These differences remained after adjusting for age and body mass index ( p<0.0005 at all sites). Overall, 41.8% of the fracture group were osteoporotic in at least one site ( T-score <-2.5 SD below the mean for young men) compared with only 10.3% of controls. This study is the first to demonstrate that men with distal forearm fractures have lower bone mineral density than their peers and a higher risk of osteoporosis.

Absorptiometry, Photon↗

The influence of back pain on balance and functional mobility in 65- to 75-year-old women with osteoporosis.

To determine whether the presence of back pain and its related disabilities are determinants of balance and functional mobility in a group of women with osteoporosis, we carried out a cross-sectional analysis of 93 community-dwelling women with osteoporosis between the ages of 65 and 75 years old. We assessed health history, anthropometrics, self-report of current physical activity level and self-report of back pain (intensity and pain-related disabilities). Balance was measured by computerized dynamic posturography and functional mobility was assessed by timed figure-of-eight test. The prevalence of back pain was high (75%) in this cohort of older women with osteoporosis. Age was the major determinant of both balance and functional mobility and accounted for 9% and 14% of the variance, respectively. After accounting for age, back pain explained an additional 9% of the variance in balance and 13% of the variance in functional mobility. The high prevalence of back pain demonstrates the importance of pain management in the treatment of osteoporosis. Furthermore, the finding of self-reported back pain as a determinant of both balance and functional mobility suggests that this measure may deserve attention when screening women with osteoporosis for fracture risk. Prospective studies are needed to determine whether pain management will improve balance and functional mobility.

Aged↗

Bone loss and recovery in regional migratory osteoporosis.

Regional migratory osteoporosis (RMO) is a migrating arthralgia of the weight-bearing joints of the lower limb associated with focal osteoporosis. Little information is available on a quantitative assessment of systemic or local osteoporosis. In this study, we report three cases of RMO in which spine, hip and whole body serial assessments of bone mass have been evaluated to outline their extent and time course of changes. Systemic osteoporosis, with a prevalent involvement of the mainly trabecular skeletal sites, was present in all the patients, with T-scores below -2.5 at both the lumbar spine and femoral neck. Bone loss in acute episodes ranged from -75.5% to -14.7% and appeared related to the severity of the episode. In acute episodes the demineralizing process affected the whole limb from the hemipelvis to the foot: the bone loss ranged from -33.6% to -3.5% at sites with prevalent trabecular composition and from -19.1% to -1.1% at sites with prevalent cortical composition. Bone recovery was complete in one episode out of six. In the other five cases, the average residual bone loss was 26% (range 13.9-32.7%). Our observations suggest that RMO occurs in subjects with systemic osteoporosis and densitometric assessment may aid in the clinical management.

Acute Disease↗

Therapy of male osteoporosis with parathyroid hormone.

Definable causes of male osteoporosis account for only about 60% of the osteoporotic population. Those for whom no etiology is readily apparent are said to have primary or idiopathic male osteoporosis. In these individuals, histomorphometric studies indicate that this is a disorder that is more typically characterized by low turnover. Although antiresorptive agents such as alendronate have been shown to increase bone mass in men, the rationale for an anabolic agent that can stimulate bone formation is clear. The most attractive anabolic agent at this time is parathyroid hormone (PTH) administered in low dosage and intermittently. Such regimens in experimental animals have been associated with marked gains in bone mass. Slovik et al. showed that parathyroid hormone can increase vertebral bone mass in men with idiopathic osteoporosis. We have conducted the first controlled, randomized, double-blind study of PTH in men with idiopathic osteoporosis. Twenty-three men, 30-68 years old (50 +/- 1.9) with Z-scores less than -2.0 were assigned to a placebo (n = 13) or treatment (n = 10) arm. After 18 months, those who received PTH showed a 13.5 +/- 3% increase in bone mass, significantly greater than the placebo group whose bone density did not change. Femoral neck bone density increased significantly by 2.9 +/- 1.5%. The distal radius site did not change. During an open label extension for an additional 12 months, there was no further increase in bone density in the lumbar spine but the femoral neck continued to show gains. Markers of bone formation and resorption increased in the PTH arm reaching a peak between 9 and 12 months of therapy and declining thereafter. Parathyroid hormone was well tolerated. These results suggest that low-dose intermittent PTH may be an efficacious therapy for men with idiopathic osteoporosis.

Adult↗

Ascorbic acid deficiency, iron overload and alcohol abuse underlie the severe osteoporosis in black African patients with hip fractures--a bone histomorphometric study.

Osteoporosis and femoral neck fractures (FNF) are uncommon in black Africans although osteoporosis accompanying iron overload (from traditional beer brewed in iron containers) associated with ascorbic acid deficiency (oxidative catabolism by iron) has been described from sub-Saharan Africa. This study describes histomorphometric findings of iliac crest bone biopsies and serum biochemical markers of iron overload and of alcohol abuse and ascorbic acid levels in 50 black patients with FNFs (29 M, 21 F), age 62 years (40-95) years (median [min-max]), and in age- and gender-matched black controls. We found evidence of iron overload in 88% of patients and elevated markers of alcohol abuse in 72%. Significant correlations between markers of iron overload and of alcohol abuse reflect a close association between the two toxins. Patients had higher levels of iron markers, i.e., siderin deposits in bone marrow (P < 0.0001), chemical non-heme bone iron (P = 0.012), and serum ferritin (P = 0.017) than controls did. Leukocyte ascorbic acid levels were lower (P = 0.0008) than in controls. The alcohol marker mean red blood cell volume was elevated (P = 0.002) but not liver enzymes or uric acid. Bone volume, trabecular thickness, and trabecular number were lower, and trabecular separation was greater in patients than in controls, all at P < 0.0005; volume, surface, and thickness of osteoid were lower and eroded surface was greater, all at P < 0.0001. There was no osteomalacia. Ascorbic acid deficiency accounted significantly for decrease in bone volume and trabecular number, and increase in trabecular separation, osteoid surface, and eroded surface; iron overload accounted for a reduction in mineral apposition rate. Alcohol markers correlated negatively with osteoblast surface and positively with eroded surface. Relative to reported data in white FNF patients, the osteoporosis was more severe, showed lower osteoid variables and greater eroded surface; FNFs occurred 12 years earlier and were more common among men. We conclude that the osteoporosis underlying FNFs in black Africans is severe, with marked uncoupling of resorption and formation in favor of resorption. All three factors--ascorbic acid deficiency, iron overload, and alcohol abuse--contributed to the osteoporosis, in that order.

Adult↗

Vitamin D therapy of osteoporosis: plain vitamin D therapy versus active vitamin D analog (D-hormone) therapy.

Normal intestinal calcium (Ca) absorption is an essential feature of bone homeostasis. As with many other organ systems, intestinal Ca absorption declines with aging, and this is one pathological factor that has been identified as a cause of senile osteoporosis in the elderly. This abnormality leads to secondary hyperparathyroidism, which is characterized by high serum parathyroid hormone (PTH) and an increase in bone resorption. Secondary hyperparathyroidism due to poor intestinal Ca absorption has been implicated not only in senile osteoporosis but also in age-related bone loss. Accordingly, in population-based studies, there is a gradual increase in serum PTH from about 20 years of age onward, which constitutes a maximum increase at 80 years of age of 50% of the basal value seen at 30 years of age. The cause of the increase in PTH is thought to be partly due to impaired intestinal Ca absorption that is associated with aging, a cause that is not entirely clear but at least in some instances is related to some form of vitamin D deficiency. There are three types of vitamin D deficiency: (1) primary vitamin D deficiency, which is due to a deficiency of vitamin D, the parent compound; (2) a deficiency of 1,25(OH)(2)D(3) resulting from decreased renal production of 1,25(OH)(2)D(3); and (3) resistance to 1,25(OH)(2)D(3) action owing to decreased responsiveness to 1, 25(OH)(2)D(3) of target tissues. The cause for the resistance to 1, 25(OH)(2)D(3) could be related to the finding that the vitamin D receptor level in the intestine tends to decrease with age. All three types of deficiencies can occur with aging, and each has been implicated as a potential cause of intestinal Ca malabsorption, secondary hyperparathyroidism, and senile osteoporosis. There are two forms of vitamin D replacement therapies: plain vitamin D therapy and active vitamin D analog (or D-hormone) therapy. Primary vitamin D deficiency can be corrected by vitamin supplements of 1000 U a day of plain vitamin D whereas 1,25(OH)(2)D(3) deficiency/resistance requires active vitamin D analog therapy [1, 25(OH)(2)D(3) or 1alpha(OH)D(3)] to correct the high serum PTH and the Ca malabsorption. In addition, in the elderly, there are patients with decreased intestinal Ca absorption but with apparently normal vitamin D metabolism. Although the cause of poor intestinal Ca absorption in these patients is unclear, these patients, as well as all other patients with secondary hyperparathyroidism (not due to decreased renal function), show a decrease in serum PTH and an increase in Ca absorption in response to therapy with 1, 25(OH)(2)D(3) or 1alpha(OH)D(3). In short, it is clear that some form of vitamin D therapy, either plain vitamin D or 1,25(OH)(2)D(3) or 1alpha(OH)D(3), can be used to correct all types of age-dependent impairments in intestinal Ca absorption and secondary hyperparathyroidism during aging. However, from a clinical standpoint, it is important to recognize the type of vitamin D deficiency in patients with senile osteoporosis so that primary vitamin D deficiency can be appropriately treated with plain vitamin D therapy, whereas 1,25(OH)(2)D(3) deficiency/resistance will be properly treated with 1,25(OH)(2)D(3) or 1alpha(OH)D(3) therapy. With respect to postmenopausal osteoporosis, there is strong evidence that active vitamin D analogs (but not plain vitamin D) may have bone-sparing actions. However, these effects appear to be results of their pharmacologic actions on bone formation and resorption rather than through replenishing a deficiency.

Aging↗

An update on the assessment of osteoporosis using radiologic techniques.

In this article, the currently available radiologic techniques for assessing osteoporosis are reviewed. Density measurements of the skeleton using dual X-ray absorptiometry (DXA) are clinically indicated for the assessment of osteoporosis and for the evaluation of therapies. DXA is the most widely used technique for identifying patients with osteoporosis. Quantitative computed tomography (QCT) is the only method, which provides a volumetric density. Unlike DXA, QCT allows for selective trabecular measurement and is less sensitive to degenerative diseases of the spine. The analysis of bone structure in conjunction with bone density is an exciting new field in the assessment of osteoporosis. High-resolution multi-slice CT and micro-CT are useful tools for the assessment of bone microarchitecture. A growing literature indicates that quantitative ultrasound (QUS) techniques are capable of assessing fracture risk. Although the ease of use and the absence of ionizing radiation make QUS attractive, the specific role of QUS techniques in clinical practice needs further determination. Considerable progress has been made in the development of MR techniques for assessing osteoporosis during the last few years. In addition to relaxometry techniques, high-resolution MR imaging, diffusion MR imaging and in-vivo MR spectroscopy may be used to quantify trabecular bone architecture and mineral composition.

Bone Density↗

Rheumatoid arthritis and osteoporosis.

Some controversial issues in the current literature in relation to osteoporosis and rheumatoid arthritis are updated and discussed. Because most studies agree that osteoporosis in postmenopausal women and in men with RA is more evident at the hip and radius than at the spine, and that the most important determinants of bone loss are disability, local disease activity, and cumulative corticosteroid dose, osteoporosis is not a common systemic extra-articular manifestation of RA. In early arthritis, periarticular osteoporosis does indeed reflect disease activity because it is closely related to the acute phase reactants, but once periarticular osteoporosis is established it is no longer a marker of disease severity. The threshold dose for corticosteroid-induced osteoporotic fractures is the cumulative rather than the actual dose. Statements based on quantitative tomography concerning the acute effects (and their reversal) of corticosteroids on bone have to be interpreted with care because of important body composition changes, in particular in bone marrow fat, during corticosteroid treatment. At present there is no evidence that anti-resorbing drugs can change the progress of RA erosions, probably because erosions are the result of non-osteoclast mediated mechanisms. Stress fractures in RA are underdiagnosed and are often confused with synovitis, and therefore it is likely that they are more frequent than commonly thought, especially in the lower limbs. Methotrexate osteopathy is known in oncological practice. Whether low dose methotrexate is toxic for bone is not clear, but a number of clinical observations suggest that the occurrence of spontaneous fractures and lower extremity pain is more frequent in methotrexate treated patients than expected. Prospective studies are necessary to confirm these impressions.

Adrenal Cortex Hormones↗

PASSCLAIM - Bone health and osteoporosis.

BACKGROUND: The EC Concerted Action PASSCLAIM aims to produce a generic tool for assessing the scientific support for health-related claims for foods and food components. AIM: The task of the ITGB Working Group was to critically evaluate the categories of scientific evidence needed to support claims in relation to bone health and osteoporosis. METHODS: A framework was developed to describe the chain of evidence that is required to link the consumption of a food or food component to bone health outcomes. Techniques available for interrogating each link in the chain were identified and their strengths and weaknesses considered. This framework was used to determine intermediate markers of health outcome with respect to osteoporosis and to debate the level of evidence that would be required to substantiate claims of enhanced function or reduced disease risk. RESULTS: Use of this framework with osteoporotic fracture as the health endpoint resulted in the following judgements based on current knowledge: 1) bone mineral density (BMD) is an intermediate marker of bone health which, for people of any age and sex, can provide evidence of enhanced function; 2) for people over 50 years living in populations with a high incidence of fracture, BMD is an intermediate marker of osteoporotic fracture risk which can provide evidence of an increased probability of reduced disease risk; 3) because osteoporosis is defined as a state of increased fracture risk due to low bone mass and deterioration in bone microarchitecture, a claim of a definite reduction in osteoporosis or fracture risk requires similar substantiation to claims that fractures are prevented or treated, including clinical trials and animal studies; 4) data from lower in the chain of evidence, such as bone turnover and calcium bioavailability, are not, by themselves, sufficiently strongly related to bone health endpoints to provide evidence of enhanced function or reduced disease risk but can provide supporting information. CONCLUSIONS: In the light of existing scientific knowledge, a framework has been developed as a tool for considering the scientific support for claims relating to bone health and osteoporosis. To provide a working example, the framework has been used to assess the current position with osteoporotic fracture as the health endpoint. This experience will contribute to the formulation under PASSCLAIM of a generic tool for assessing the scientific support of health claims on foods.

Animals↗

[Strontium ranelate: a novel concept for the treatment of osteoporosis].

The di-strontium salt strontium ranelate, a novel orally active agent consisting of two atoms of stable strontium and the organic moiety ranelic acid, has been developed for the treatment of osteoporosis. It has been shown to enhance osteoblastic cell replication and increase collagen synthesis while decreasing pre-osteoclast differentiation and bone-resorbing activity of mature osteoclasts in vitro. Studies performed in healthy animals have shown that strontium ranelate not only increases bone mass at various skeletal sites but also improves mechanical properties of femoral, humeral and vertebral bones. In estrogen-deficient animals, strontium ranelate effectively inhibits increased bone resorption while maintaining bone formation. Similar results have been obtained from studies in hind limb-immobilized animals. Strontium ranelate has been investigated in a large phase III program which includes two extensive multinational, randomized, double-blind, placebo-controlled clinical trials for the treatment of severe postmenopausal osteoporosis. Before inclusion in these two studies, patients were subjected to a run-in study in order to initiate normalization of their calcium and vitamin D status. The SOTI study, aimed at assessing strontium ranelate's effect on the risk of vertebral fractures, revealed a significant reduction in the risk of new vertebral fractures in the group treated with strontium ranelate. The TROPOS study, which aimed at evaluating the effect of strontium ranelate on nonvertebral fractures, showed a significant reduction in the risk of new nonvertebral fractures and also, in a high-risk subgroup, a significant reduction in the risk of hip fractures. In both studies, the reduction in fracture risk was accompanied by an increase in bone mineral density. The increase remained significant also after correction of the bone mineral density for the higher atomic mass of strontium compared to calcium. Furthermore, an increase in serum levels of a bone formation marker and a decrease in serum levels of a bone resorption marker were observed. The spectrum of side effects comprised mild diarrhea, particularly within the first weeks of treatment, and also a slightly increased risk of venous thromboembolic events. Strontium ranelate thus appears to be a new, effective treatment to prevent fractures in postmenopausal osteoporosis with a novel mechanism of action. It can be expected for the near future that strontium ranelate will also be evaluated for other types of osteoporosis, such as male osteoporosis.

Animals↗

Trochanteric hip fracture in an elderly patient with leprosy during osteoporosis treatment with risedronate and alfacalcidol.

There is no well-established treatment for osteoporosis in male patients with leprosy, because no clinical trials have examined the efficacy of treatment on bone mineral density (BMD) or fracture incidence in patients with leprosy. In this study, we report a case of osteoporosis in a man with leprosy, treated by oral administration of risedronate and alfacalcidol. An 82-year-old man with leprosy presented to our hospital with chronic back pain, due to osteoporosis, in July 2002. To prevent the progression of osteoporosis, oral administration of risedronate and alfacalcidol was started for this patient. An increase in forearm BMD and a decrease in the level of urinary crosslinked N-telopeptides of type I collagen (NTx) were observed in January 2003. The patient suffered a trochanteric fracture of the proximal femur at the end of March 2003. Surgical treatment with a sliding-screw plate was performed 5 days after the injury. Complete bony union of the right proximal femur was confirmed by radiography in July 2003. The above findings suggested that the treatment with risedronate and alfacalcidol contributed to the increase in BMD; however, the treatment did not prevent fracture due to osteoporosis in this male patient with leprosy.

Aged↗

Clinical factors as predictors of the risk of falls and subsequent bone fractures due to osteoporosis in postmenopausal women.

In Japan, the "bedridden state" is one of the most serious problems the aged face, and it is becoming a social problem. The main causes of the bedridden state are cerebrovascular disorders and bone fractures following falls. The purpose of this study was to predict risk factors for falls and resultant bone fracture due to osteoporosis. We explored mobility parameters for possible fall prevention. In order to examine the correlation between the risk of falling and resultant bone fracture due to osteoporosis, logistic regression analysis was performed between bone mass (independent variable) and various factors dependent variables: body mass index [BMI], body fat percentage, atherogenic index, presence of transformation-related osteoarthritis of knee, presence of transformation-related osteoarthritis of spine, maximum step length, single-leg stance with open eyes, and hip-joint flexion motion angle); predictive factors were then examined. Predictive factors were determined by the stepwise method. Subjects who could not perform the "single-leg stance with open eyes" test had a risk of falling and bone fracture 2.49 times as large as that of subjects who could. The "single-leg stance with open eyes" test may be considered a useful method for the early detection of the risk of falling and bone fracture associated with osteoporosis. As a first step to identify factors predicting the occurrence of falls and bone fractures due to osteoporosis, we intended to discover an indicator that would help to detect incipient osteoporosis.

Accidental Falls↗

The change of bone mineral density in secondary osteoporosis and vertebral fracture incidence.

Causes of secondary osteoporosis are diverse, and bone changes in this condition have been elucidated less than those in primary osteoporosis. In this study, bone mineral density (BMD) was measured in the lumbar spine, distal and proximal sites of the radius, and calcaneus in representative disorders that cause secondary osteoporosis to evaluate its changes. Also, the incidence of nontraumatic vertebral fracture was examined. The subjects were 80 patients with rheumatoid arthritis, 50 patients undergoing glucocorticoid (steroid) therapy, 20 patients with chronic hepatitis, 24 patients with liver cirrhosis, 14 patients with primary biliary cirrhosis (PBC), 26 patients with diabetes mellitus, and 20 postgastrectomy patients; all were ambulatory female outpatients. Two hundred females with primary osteoporosis were examined as a control group. The reproducibility of the measurement of the BMD was satisfactory at about 3% by all methods of measurement employed. Concerning changes in BMD, periarticular trabecular bone density was most markedly reduced in the rheumatoid arthritis group. The patients receiving steroid therapy showed the greatest decreases in the trabecular bone mineral density at the distal 4% of the radius and lumbar spinal BMD. In addition, the threshold of vertebral fracture was higher in those undergoing steroid therapy than in those with primary osteoporosis. The patients with PBC showed the greatest decreases in BMD among patients with chronic liver disorders, and no decrease in BMD was noted in the chronic hepatitis group. BMD was reduced only in the radius in the patients with diabetic mellitus, and it was generally reduced in the postgastrectomy patients. BMD of the calcaneus was not reduced in any group.

Adrenal Cortex Hormones↗