Superiority of alfacalcidol compared to vitamin D plus calcium in lumbar bone mineral density in postmenopausal osteoporosis.

In a randomized multicenter, double-blind, double-dummy, parallel group study a comparison of the efficacy and safety of 1 microg alfacalcidol to 880 IU vitamin D plus calcium carbonate (1 g calcium) once daily per os was performed on 148 postmenopausal osteoporotic Caucasian patients with normal vitamin D serum levels for 18 months. Bone mineral density (BMD) was measured at baseline, 12 and 18 months. Safety parameters were followed during the entire study period. Sixty-nine (90.8%) in the alfacalcidol group and 67 (93.1%) in the vitamin D group were included in the ITT analysis. Lumbar BMD in the alfacalcidol group increased by 0.017 g/cm2 (2.33%) and 0.021 g/cm2 (2.87%) from baseline (P<0.001) at 12 and 18 months, respectively, whereas in the vitamin D plus calcium group the increase was 0.005 g/cm2 (0.70%) from baseline (N.S.) at both 12 and 18 months. The higher changes from baseline in the alfacalcidol group, as compared to the changes in the vitamin D plus calcium group at both 12 and 18 months, were found to be statistically significant (P=0.018, 0.005). A small increase of mean femoral BMD was achieved in both groups (N.S.). Adverse events were similar in both groups. No significant differences were noted between the groups in serum calcium. In conclusion, alfacalcidol was found to be superior in significantly increasing lumbar BMD as compared to vitamin D plus calcium while safety characteristics were found to be similar in both treatments.

[Longitudinal study on osteoarthritis and bone metabolism]. / Studio longitudinale su artrosi e metabolismo osseo.

OBJECTIVE: The relationship between Osteoarthritis (OA) and Osteoporosis (OP) is not well defined due to lacking in longitudinal data, mainly regarding correlations between biochemical factors and OA incidence. Aim of this paper was to investigate the predictive value for OA incidence of bone mass variations and of selected biochemical markers in healthy women participating in a population-based longitudinal study carried out in Naples (Italy). SUBJECTS AND METHODS: High completion rate (85.2%) and statistically adequate sample size were obtained: 139 women (45 to 79 years of age) were examined and follow up visit was performed after two years (24+/-2 months), following the same protocol. Patients underwent medical examination, questionnaire, anthropometric measurements, blood sampling and urine collection. Bone mineral density (BMD) measurement was performed by dual energy X-ray absorptiometry (DEXA) at the lumbar spine (L1-L4) and femoral neck. Radiographs of dorsal and lumbar spine in lateral view were performed at basal and at 24 months visits; a team of three experts scored radiographs using Kellgren and Lawrence grading. RESULTS: The score was calculated for two individual radiographic features (narrowing of the joint space, presence of osteophytes) and as a global score. Results show a relevant percentage, 23% up, of subjects presenting both OA and OP. In the cross-sectional study the presence of osteophytosis correlates with anthropometric variables and PTH levels. In the longitudinal study results show a correlation between serum vitamin D and delta score for osteophytosis (beta=0.02 p<0.05). CONCLUSIONS: Data obtained outline the importance of further studies on the pathogenetic link between OA and bone metabolism.

Bone mineral density and bone markers in hypogonadotropic and hypergonadotropic hypogonadal men after prolonged testosterone treatment.

After prolonged treatment (76.4+/-10 and 70.1+/-12.3 months, respectively) (mean+/-SE) with testosterone enanthate (250 mg i.m. every 3 weeks), bone mineral density (BMD) and bone metabolism were evaluated in 12 patients (aged 29.3+/-1.4 yr) affected by idiopathic hypogonadotropic hypogonadism (IHH), in 8 patients (29.6+/-2.6 yr) affected by Klinefelter's syndrome (KS), and in 10 healthy men (30.6+/-1.7 yr) matched according to age and BMI. Spinal BMD in IHH was significantly lower than in controls (0.804+/-0.04 vs 1.080+/-0.01 g/cm2; p<0.001), while there was no difference in neck BMD (0.850+/-0.01 vs 0.948+/-0.02 g/cm2). Neither spinal (0.978+/-0.05 g/cm2) nor neck (0.892+/-0.03 g/cm2) BMD in KS were significantly different from controls. Six IHH and one KS subjects were osteoporotic, while 6 IHH and 2 KS subjects were osteopenic. A significant inverse correlation was found between spinal BMD and age at the treatment onset in IHH (r=-0.726, p=0.007). In IHH there were significant increases in bone formation (alkaline phosphatase=318.3+/-33.9 vs 205.4+/-20.0 IU/l; osteocalcin=13.44+/-1.44 vs 8.57+/-0.94 ng/ml; p<0.05) and in bone resorption (urinary cross-linked N-telopeptides of type I collagen=149.1+/-32.3 vs 47.07+/-8.4 nmol bone collagen equivalents/mmol creatinine; p<0.05) compared to controls, while such differences were not present in KS. Our results outline the importance of BMD evaluation in all hypogonadal males. Nevertheless, bone loss is a minor characteristic of KS, while it is a distinctive feature of IHH. Therefore, early diagnosis and age-related replacement therapy coupled with a specific treatment for osteoporosis could be useful in preventing future severe bone loss and associated skeletal morbidity.

Intramuscular clodronate in nonresponders to oral alendronate therapy for osteoporosis.

OBJECTIVE: Oral alendronate is effective in increasing bone mineral density (BMD) and in reducing fracture incidence. However, a large proportion of patients under treatment do not show significant changes in BMD, or even bone loss. Incorrect administration, low intestinal absorption, and poor compliance are among factors that may account for this effect. In this subgroup of patients we evaluated whether intramuscular (im) clodronate increased the number of responders. METHODS: Using an open case-control design we studied 60 postmenopausal osteoporotic women (mean age 58.9 years +/- 4.8 SD) after one year of therapy with oral alendronate who had an increase in BMD that was lower than the in vivo densitometry measurement error (2%). Subjects were divided into 2 groups: the first continued aledronate treatment (AL group); the second began weekly im injections of clodronate 100 mg (CL group). BMD measurements were performed at the right femoral neck by the same operator, using dual energy x-ray absorptiometry. RESULTS: After 12 months of therapy the prevalence of responders (increase in BMD > 2%) was 40% in the AL group and 66% in the CL group (prevalence rate ratio = 1.65; 95% CI 1.25-2.04). The treatment group was the only variable that showed a significant correlation with being a responder (beta = 1.13; p = 0.03), as analyzed by multiple logistic regression to account for the effect of confounding factors. In the CL group the difference in the mean value of BMD between time T0 and time T+12 was greater than in the AL group, but did not reach statistical significance. The mean percentage variation of BMD was significantly greater in the CL group (+3.21%) compared to the AL group (+0.98%) (p < 0.001, t test) (f value = 8.4; p < 0.01, by multiple linear regression analysis using the same covariates). CONCLUSION: Treatment with weekly intramuscular injection of clodronate in nonresponders to oral alendronate showed a higher number of subjects with a significant increase in BMD, compared to continuation of therapy with alendronate.

Are there differences in methotrexate kinetics between responding and nonresponding patients with rheumatoid arthritis?

OBJECTIVE AND STUDY DESIGN: The purpose of this study was to investigate the presence of a correlation between methotrexate pharmacokinetics and clinical efficacy in patients with rheumatoid arthritis. PATIENTS AND METHODS: The study was carried out in 29 patients with rheumatoid arthritis. The patients received intramuscular methotrexate (MTX) 7.5mg once a week for 8 weeks. Before and 0.5, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the first administration, MTX serum concentrations were measured and pharmacokinetic investigations were carried out. The clinical status of the disease was evaluated before and after 8 weeks of therapy. In addition, before and after 2 and 8 weeks of treatment, the patients were monitored for a complete biochemical profile. After 8 weeks of treatment, on the basis of improvement in clinical parameters, the patients were designated responders or nonresponders. RESULTS: A clinical response was obtained in 62% of patients (18 patients responded and 11 did not) and was associated with a low incidence of adverse effects. There were no differences in the pharmacokinetic parameters of MTX between the 2 groups of patients (responders vs nonresponders), except that t(max) was significantly higher in nonresponders than in responders (p < 0.05). CONCLUSIONS: These data confirm the efficacy and tolerability of low dose MTX in patients with rheumatoid arthritis in the short term, but appear to exclude a relationship between MTX kinetics and clinical response.

Bone mineral density in premenopausal women receiving levothyroxine suppressive therapy.

Osteoporosis is a well-known complication of thyrotoxicosis. Prolonged subclinical hyperthyroidism due to L-thyroxine treatment has been associated with reduced bone mass and thus with the potential risk of premature development of osteoporosis. The aim of this study was to assess the effect of a chronic L-thyroxine suppressive treatment on bone mineral density (BMD) in a group of premenopausal women. Forty consecutive patients (mean age +/- SE = 40.95 +/- 1.56 years) affected by non-toxic goiter underwent bone mineral densitometry (dual energy X-ray absorptiometry; DEXA) of the lumbar spine (L1-L4) and right femoral neck. At the time of the study the patients had been under thyroid stimulating hormone (TSH) suppressive therapy for 74.95 +/- 10.34 months (range 17-168 months). Baseline levels of free thyroxine (fT4), free triiodothyronine (fT3), TSH, calcium and phosphorus were measured and correlated with BMD. The age of starting, duration of treatment, main daily dose, cumulative dose of treatment and body mass index (BMI) were also correlated with BMD. Statistical analysis was performed by multiple linear regression. BMD among female patients was not significantly different from that of the general population matched for age and sex. With the use of the regression model, no significant correlation was found between BMD and the variables considered. In conclusion, our data suggest that L-thyroxine suppressive therapy, if carefully carried out and monitored, has no significant effect on bone mass.

Peripheral body fat has a protective role on bone mineral density in elderly women.

OBJECTIVES: To determine whether bone mineral density is lower in women living in homes for the elderly as compared to free dwelling control subjects, and to investigate factors affecting possible differences. This is the first study with this objective as the primary aim. DESIGN: Case-control study. SUBJECTS AND METHODS: Institutionalised independent elderly women (n = 22, mean age = 75.1 y+/-6.43 s.d.) randomly selected in a home for the elderly and 22 age-matched control women randomly selected from a sample representative of the independent non institutionalised local population who underwent dual energy X-ray absorptiometry (DXA) at the lumbar spine and right femoral neck; anthropometric measurements (height, weight, subscapular and triceps skinfold thickness); general questionnaire. RESULTS: Mean bone mineral density at the femoral neck was 0.618 g/cm2 (+/-0.130s.d.) in institutionalised women and 0.709 g/cm2 (+/-0.106 s.d.) in controls (P = 0.02, t-test). Controlling for confounding factors in the analysis of covariance, triceps skinfold thickness and living in a home for the elderly turned out to be significant determinants of bone mineral density. CONCLUSION: When compared to free dwelling control subjects, institutionalised women show lower bone density, that is the main risk factor for fracture. Reduced peripheral body fat was significantly associated with the low bone mineral density observed. Health programs aimed at decreasing the incidence of fractures among institutionalised subjects will also have to consider the effect of nutritional or life style factors that reduce peripheral body fat.

[Modifications in diagnosis and therapy of osteoporosis after bone densitometry]. / Modifica di diagnosi e terapia per l'osteoporosi dopo esecuzione di un esame densitometrico.

The cost-benefit ratio of diagnostic procedures has become a major problem: in particular, the expense of computerized bone mineral densitometry for osteoporosis diagnosis has brought this issue to public attention. To avoid a procedure considered costly, non-specialists often rely on standard radiography alone for diagnosis. In this study, we evaluated the percent of cases in which densitometry modified diagnosis and therapy based solely on radiographic findings. Over a 10-month period, we recruited 133 consecutive post-menopausal patients (average age 58.3 years, average time since menopause 12 years) who had never undergone densitometry. Bone density at the lumbar (L1-L4) or femoral (non-dominant) level was measured with dual energy X-ray absorptiometry. The average time between densitometry and the last radiographic examination was 13.6 months. Ninety-one patients (68.4%) had a change in diagnosis following densitometry. In 42 cases (31.6%), the previous diagnosis remained unchanged (prevalence ratio 2.2; 95% confidence interval 1.6 to 2.7). Therapy was changed in 75.2% of the cases (100 patients) and remained the same in 24.8% (33 patients; prevalence ratio 3.0; 95% confidence interval 2.3 to 3.7). Our data underscore the importance of densitometry in yielding quantitative data that are utilizable during follow-up and able to support osteoporosis diagnosis and therapy.

Reversibility of joint thickening in acromegalic patients: an ultrasonography study.

Axial and peripheral arthropathy affects the majority of patients with acromegaly, being a leading cause of morbidity and functional disability. Treatment with octreotide (OCT) improves symptoms and signs of acromegalic arthropathy, but objective detection of structural changes in bone and cartilage has not been reported to date. This open prospective study was designed to evaluate the effect of a long term treatment with OCT on acromegalic arthropathy assessed by ultrasonography examination. Articular cartilage thicknesses of shoulder, wrist, and knee as well as sizes of heel tendons were measured in 30 acromegalic patients (18 with active and 12 with inactive disease) and 18 sex-, age-, and body mass index-matched healthy subjects. The thicknesses of shoulder, wrists and knees articular cartilages and that of heel tendons were significantly increased in patients with active acromegaly compared to those in healthy subjects (P < 0.01). With the exception of shoulder cartilage, significant increases in wrist and knee cartilages (P < 0.01) and right and left heel tendon sizes (P < 0.05) were found in patients with active compared to those with inactive disease. After 6 months of OCT treatment, a significant decrease in shoulder, wrist, and left knee articular cartilage was found (P < 0.001). No significant change was recorded in right knee cartilage or heel tendon size. The decrease in thickness of shoulder and wrist cartilages was more pronounced than that measured at the level of left knee (26.3 +/- 3.3% and 27.2 +/- 4.2% vs. 14.2 +/- 4.2%, respectively; P < 0.05). Ultrasonography is able to reveal articular involvement in acromegalic patients and may be useful to monitor the effect of treatment.

Epidemiology of osteoporosis in women in southern Italy.

Studies on the distribution of bone mineral density (BMD) values in different age groups and in different populations are valuable for understanding the causes of the appreciable geographical variability in fracture incidence. We studied a population of southern Italy in an area where the incidence of hip fracture had been previously estimated. With a completion rate of 85%, we recruited a group of 264 women between 45 and 79 years of age, representative of non-institutionalized and active women in the population, and measured bone density both at the lumbar spine (L1-L4) and at the right femoral neck using a dual X-ray absorptiometry (DEXA) system. We report the age group distribution of BMD in this population. The elderly showed higher mineralization, as compared to an international pooled sample. The prevalence of osteoporosis among women of 50-79 years of age was 40%; the rate changed according to the measurement site. Our results show that a large proportion of women would not have been diagnosed as having osteoporosis if we had relied on a single measurement site. A very low percentage of cases (as low as 4% in the 50-59 years age group) was diagnosed at both sites. The lack of concordance in BMD estimate between measurement sites is significant at younger ages, with an almost dichotomous distribution of cases diagnosed either at the lumbar or femoral site, suggesting the hypothesis that distinct patterns of bone involvement and bone mass lowering exist and all eventually lead to systemic involvement. Longitudinal follow-up of this population should help address some of the questions raised by these results.

Randomized trial of effect of cyclical etidronate in the prevention of corticosteroid-induced bone loss. Ciblos Study Group.

Osteoporosis is a well-recognized adverse effect of corticosteroid therapy. This study aimed to investigate the effect of etidronate, intermittent cyclical therapy, in the prevention of corticosteroid-induced bone loss. Patients with various medical conditions starting high-dose corticosteroid therapy were enrolled in the study. The treatment had to be expected to continue for at least 12 months with the initial 90 days at a mean daily dose of at least 7.5 mg of prednisone, with subsequent treatment of at least 2.5 mg/day. One hundred seventeen patients were randomly assigned oral etidronate 400 mg/day, or placebo, for 14 days, followed by 76 days of oral calcium carbonate (500 mg elemental calcium), cycled over 12 months. The primary outcome measure was the difference in percent change from baseline in bone mineral density of the lumbar spine between the groups at the end of year 1. Secondary measures included changes in femur bone density and in biochemical markers of bone remodeling. The mean (+/- SEM) lumbar spine bone density changed 0.30 +/- 0.61% and -2.79 +/- 0.63% in the etidronate and placebo groups, respectively. The mean difference between groups after 1 yr was 3.0 +/- 0.84% (P = 0.004). The changes in the femoral neck and great trochanter were not different between the groups. There was a decrease in pyridinium crosslinks, significant from baseline at both 6 and 12 months, in the etidronate group. Osteocalcin increased in the placebo group, and difference between groups was -25.07 +/- 14.89% (P = 0.032) and -34.68 +/- 19.77% (P = 0.051), at 6 and 12 months respectively. There was no significant difference between the groups in number of adverse experiences, including gastrointestinal disorders. Etidronate intermittent cyclical therapy prevents lumbar vertebral bone loss in patients starting high-dose corticosteroid therapy.

Efficacy and tolerability of ketoprofen 200 mg controlled-release cps vs indomethacin 50 mg cps in patients with symptomatic hip osteoarthritis. A multicentre study.

BACKGROUND: An open-label, randomised, multicentre study was carried out to compare the efficacy and tolerability of indomethacin capsules and ketoprofen controlled-release capsules in the symptomatic treatment of coxarthrosis. MATERIALS AND METHODS: 113 out-patients were enrolled: 57 were assigned to receive indomethacin 50 mg twice daily and 56 ketoprofen 200 mg once daily for 4 weeks. RESULTS: Indomethacin and ketoprofen proved equally effective in relieving osteoarticular pain and stiffness and in improving the quality of life of patients. There was essentially no difference as to gastrointestinal adverse events which occurred in 25% of patients on indomethacin and in 27% of those on ketoprofen. Indomethacin caused more non-gastrointestinal untoward effects, especially CNS effects (headache and dizziness: 11%) which were not observed with ketoprofen. Indomethacin was discontinued because of adverse events in a larger proportion of patients (20%) than ketoprofen (11%).

The classification of psoriatic arthritis: what will happen in the future?

Some patients with psoriasis have articular involvement that falls within the spectrum of seronegative spondyloarthropathies. This form of arthritis has been classified by Moll and Wright into five clinical subsets. Recently this classification has been contested. We review the historical evolution of the concept of psoriatic arthritis and discuss its clinical spectrum.

The arthritis of coeliac disease: prevalence and pattern in 200 adult patients.

Arthritis has often been alluded to as an extra-intestinal clinical manifestation of coeliac disease, but definitive data regarding its prevalence are still lacking. We therefore evaluated the overall prevalence of articular involvement in 200 consecutive adult coeliac patients attending routine gastroenterology follow-up and in 40 controls, and determined whether the prevalence and pattern of articular involvement varied according to the dietary status. An arthritis was present in 26% of patients and in 7.5% of controls, prevalences ranging from 41% in patients on a regular diet to 21.6% in patients on a gluten-free diet (P < 0.005). Arthritis was peripheral in 19 patients, axial in 15 and an overlap of both in 18 subjects. These data suggest that arthritis is much more common than previous reports have indicated, particularly in patients receiving an appropriate dietary regimen, and support the need for combined gastrointestinal and rheumatological follow-up in coeliac patients.

Slow progression of joint damage in early rheumatoid arthritis treated with cyclosporin A.

OBJECTIVE: To evaluate the ability of low-dose cyclosporin A (CsA) to control radiologic disease progression, and to assess the clinical efficacy and tolerability of CsA, compared with conventional disease-modifying antirheumatic drugs (DMARDs), in patients with early active rheumatoid arthritis (RA). METHODS: In this long-term, multicenter, prospective, open, blinded end point, randomized trial, 361 consenting patients with early (<4 years since diagnosis) active RA were enrolled. Of the eligible patients, 167 were treated with CsA at 3 mg/kg/day, and 173 with DMARDs. The decision to use conventional antirheumatic drugs as controls was based on the fact that joint erosion could be expected to occur after 1 year regardless of the type of DMARD being used. The possibility of switching therapies in both groups was intended to keep the largest possible number of patients in the study. RESULTS: Blinded evaluation of hand and foot radiographs after 12 months of treatment showed that CsA led to a significant (P < 0.001) delay in the mean +/- SD progression in the eroded joint count (1.3 +/- 3.1 versus 2.4 +/- 3.0 for the control group) and in the joint damage score (3.6 +/- 8.9 versus 6.9 +/- 9.1 for the control group), both measured by the Larsen-Dale method. When only the patients without erosion at baseline were considered (37 in the CsA-treated group and 54 in the control group), erosion appeared in only 10.8% of the CsA-treated patients, but in 51.8% of the controls (P = 0.00005). Low-dose CsA was as effective as traditional DMARDs in controlling clinical symptoms. Maintenance on the initially prescribed treatment regimen ("survival on treatment") was also better at 12 months with CsA than with DMARDs (89.2% versus 77.5%; P = 0.002). The tolerability of CsA was acceptable. CONCLUSION: These 12-month results suggest that low-dose CsA decreases the rate of further joint damage in previously involved joints as well as the rate of new joint involvement in previously uninvolved joints, in patients with early RA.

Diffuse idiopathic skeletal hyperostosis (DISH): a retrospective analysis.

Diffuse idiopathic skeletal hyperostosis (DISH) is a skeletal disease characterized by ligamentous ossification of the anterolateral side of the spine. The radiographs of the spine of 69 patients (22 males, 47 females, mean age 64.97 +/- 8.83 years) affected by DISH according to Resnick's criteria were selected. A lower rate of lumbar spine involvement (71%) and a different distribution between sexes were demonstrated, as compared to the data from the literature. Data on relationships among extent of hyperostosis, occupation and metabolic disorders suggest that an important role might be played by the exposure to microtrauma, while, in subjects affected by a metabolic disorder, this condition would represent a prevalent pathogenetic factor. These data underline some peculiarities in the clinical picture of DISH in the population from Campania, that could depend on genetic factors.

Determinants of bone mineral density in immobilization: a study on hemiplegic patients.

Osteoporosis that develops during immobilization is a severe condition that confers increased risk of fractures with their burden of mortality and disability. The aim of this study was to investigate the determinants of immobilization osteoporosis. As a model of this condition we studied hemiplegic subjects, measuring bone mineral density in the paralyzed lower limb as compared with the non-paralyzed one. In spite of the limits related to the loss of nervous stimulation, this model offers the advantage of a proper control for the complex genetic and environmental cofactors involved. We examined 48 hemiplegic subjects (31 men, 17 women in menopause) admitted consecutively over a 9-month period. Mean length immobilization was 10.9 months for men (range 1-48 months) and 7.8 months for women (range 1-40 months). The average time since menopause was 14.9 years (range 1.7-23.9 years). For each subject the following were performed: questionnaire, medical examination, anthropometric measurements, evaluation of the scores for spasticity and for lower limb motor capacity in order to account for the different degrees of disability among patients. Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA) at both femoral necks. For each patient we defined a percentage difference in bone loss between the paralyzed and non-paralyzed limb. Regression coefficient were calculated by multiple logistic regression. There was significant bone loss in the paralyzed limb in both sexes, accounting for up to 6.3% in women. Multiple regression analysis showed that the degree of bone loss depends significantly and directly on the length of immobilization, even when controlling for age and sex in the regression model (R = 0.193, p = 0.034). However, when time since menopause was included in the regression model, with length of immobility as a covariate, it was the only significant determinant of bone loss (R = 0.312, p = 0.039). No additional factors were observed among men. No differences were shown with regard to anthropometric measurements or functional scores. Length of immobilization accounts only for a small fraction of bone loss, which does not exceed 5% of the total variance. Our data show that postmenopausal women should be considered at highest risk for osteoporosis in cases of immobility and that different factors, other than length of immobility, might come into play in determining bone loss in this condition.

[The extremely low incidence of proximal femoral fractures due to osteoporosis in the population on the island of Ischia]. / Rilievo di un'incidenza estremamente bassa di fratture del femore prossimale da osteoporosi nella popolazione dell'isola di Ischia.

We present the raw data from a study done on the incidence of osteoporotic hip fractures on Ischia, an island facing the Bay of Naples. Its 43,975 inhabitants form a well-defined, stable and homogeneous population. Since no air transportation to the mainland is available for residents, acute health care is provided by the sole local hospital. We carried out a discharge data survey by reviewing the hospital medical records from 1980-1989. During that decade, 148 residents (111 women, 37 men) had new hip fractures. The age-sex adjusted incidence for the population aged 50 years or more was 170.3 cases/100,000/year [95% confidence interval (CI) = 144.8-195.9] (women = 241.4 with 95% CI = 211.0-271.9; men = 79.4 with 95% CI = 62.0-96.9). Age-specific rates increased with age and were higher among women only over 60 years old. On the basis of the 1981 census and comparison of age-adjusted rates, we determined that incidence rates of these fractures for men and women on Ischia are among the lowest in the world: Ischian men have a hip fracture incidence second only to that of South African Bantu males. The female/male ratio on the island, one of the highest reported, is 3.05:1. Our data suggest that further studies on Ischia may provide important clues regarding risk and/or protective factors for hip fracture.