Paul J. Kelly

Prevention of corticosteroid osteoporosis. A comparison of calcium, calcitriol, and calcitonin.

BACKGROUND Prolonged corticosteroid therapy increases the risk of osteoporosis and fracture. We studied whether corticosteroid-induced osteoporosis could be prevented by treatment with calcium, calcitriol (1,25-dihydroxyvitamin D3), and calcitonin. METHODS One hundred three patients starting long-term corticosteroid therapy were randomly assigned to receive 1000 mg of calcium per day orally and either calcitriol (0.5 to 1.0 microgram per day orally) plus salmon calcitonin (400 IU per day intranasally), calcitriol plus a placebo nasal spray, or double placebo for one year. Data on treatment efficacy were available for 92 of these patients. Bone density was measured every four months for two years by photon absorptiometry. There were no significant differences between groups with respect to age, underlying disease, initial bone density, or corticosteroid dose during the first year. RESULTS Calcitriol (mean dose, 0.6 microgram per day), with or without calcitonin, prevented more bone loss from the lumbar spine (mean rates of change, -0.2 and -1.3 percent per year, respectively) than calcium alone (-4.3 percent per year, P = 0.0035). Bone loss at the femoral neck and distal radius was not significantly affected by any treatment. In the second year, lumbar bone loss did not occur in the group previously treated with calcitonin plus calcitriol (+0.7 percent per year), but it did occur in the group given calcium alone (-2.3 percent per year). The calcitriol group also lost lumbar bone (-3.6 percent per year) but received more corticosteroid in the second year than the other two groups. CONCLUSIONS Calcitriol and calcium, used prophylactically with or without calcitonin, prevent corticosteroid-induced bone loss in the lumbar spine.

Symptomatic Fracture Incidence in Elderly Men and Women: The Dubbo Osteoporosis Epidemiology Study (DOES)

This longitudinal population-based study documents the incidence of all symptomatic fractures from 1989 to 1992 in an elderly, predominantly Caucasian population of males and females (⩾60 years as at 1 January 1989) living in the geographically isolated region of the city of Dubbo, NSW, Australia. Fractures were ascertained by reviewing reports from all radiology services in the region. There were 306 fractures in 271 patients during the study period representing 11 401 person-years of observation. In the 60–80 year age group only 10% of fractures involved the hip, while in the over-80 age group this proportion rose to 41%. Incidence of distal forearm, hip and total fractures increased exponentially in both sexes with increasing age. Rib fractures were relatively common, with incidence rates for rib fractures similar to those for humeral fractures. Overall fracture incidence was 2685 per 100000 person-years (males 1940 per 100000 and females 3250 per 100000). Residual lifetime fracture risk in a person aged 60 years with average life expectancy was 29% for males and 56% for females. Symptomatic fracture rates with the improved methodology in this study were higher than previously reported in both elderly males and females, with a marked preponderance of non-hip fractures in the 60–80 year age group. These symptomatic fractures have previously been underestimated, if not largely ignored, in public health approaches including cost—benefit analyses of osteoporosis prevention and treatment. Total fracture risk during later life is substantial, with fractures other than hip fractures constituting the majority of morbid fracture events, especially in the 60–80 year age group.

Progressive loss of bone in the femoral neck in elderly people: longitudinal findings from the Dubbo osteoporosis epidemiology study

Abstract Objectives: To determine prospectively the rates of change in bone mineral density in elderly people and to examine the relation between lifestyle and demographic factors and these rates of change. Design: Longitudinal population based study. Setting: Dubbo, New South Wales, Australia. Subjects: Representative sample (n=769) of residents aged >=60 on 1 January 1989. Main outcome measure: Rates of change in bone mineral density measured prospectively (mean scan interval 2.5 years) at the femoral neck and lumbar spine by dual energy x ray absorptiometry. Results: Summary rates of loss in the femoral neck were 0.96% per year (95% confidence interval 0.64% to 1.28%) in women and 0.82% per year (0.52% to 1.12%) in men. Importantly, rates of loss at the femoral neck (both percentage and absolute) increased in both sexes with advancing age. No significant loss was evident in either sex at the lumbar spine, probably because of coexistent osteoarthritis. Lifestyle factors had only modest effects on rates of loss at either site. Conclusions: These data show that bone density of the femoral neck declines at an increasing rate in elderly people, and as this site is predictive of fracture suggest that treatment to minimise bone loss may be important even in very elderly people.

Direct clinical and welfare costs of osteoporotic fractures in elderly men and women.

Osteoporosis is an increasing health care problem in all aging populations, but overall direct costs associated with the total fracture burden of osteoporosis remain uncertain. We have examined direct costs associated with 151 osteoporotic fractures occurring between 1989 and 1992 in a large cohort of elderly men and women followed prospectively as part of the Dubbo Osteoporosis Epidemiology Study. The median cost of hospital treated fractures was

Influence of vitamin D receptor genotype on bone mineral density in postmenopausal women : a twin study in Britain

A10 511 per fracture and for fractures treated on an outpatient basis

Interaction of genetic and environmental influences on peak bone density

A455 in 1992 Australian dollars. Femoral neck fractures were the most expensive fractures (

Obesity Is an Important Determinant of Baseline Serum C-Reactive Protein Concentration in Monozygotic Twins, Independent of Genetic Influences

15984 median cost). There was no significant difference in costs between men and women for either hospital- or outpatient-treated fractures. Rehabilitation hospital costs comprised the largest proportion of costs (49%) for hospital-treated fractures. Community services comprised the major cost (40%) of outpatient-treated fractures. Univariate predictors of costs were quadriceps strength and bone density, although multivariate analysis showed quadriceps strength to be the best overall predictor of costs. The predicted annual treatment costs in Australia for atraumatic fractures occurring in subjects ⩾60 years was

Dietary calcium, sex hormones, and bone mineral density in men.

A779 million or approximately

Prevalent vertebral deformities: Relationship to bone mineral density and spinal osteophytosis in elderly men and women

A44 million per million of population per annum. Estimated total osteoporotic fracture-related costs for the Australian population were much higher than previously reported. The majority of direct costs (95%) were incurred by hospitalized patients and related to hospital and rehabilitation costs. Extrapolation of these data suggests that the direct costs for hip fracture alone will increase approximately twofold in most Western countries by 2025. Improving the cost-effectiveness of treating osteoporotic fractures should involve reduced hospitalization and/or greater efficiency in community rehabilitation services. The costs of various approaches to osteoporosis prevention must be placed into the context of these direct costs and prevention should target men as well as women.

Genetic and Environmental Correlations Between Bone Formation and Bone Mineral Density: A Twin Study

Abstract Objectives: To investigate the possible association between vitamin D receptor genotype and bone mineral density in a large group of postmenopausal twins. Design: Cross sectional twin study. Setting: Twin population based in Britain. Subjects: 95 dizygotic (non-identical) pairs of twins and 87 monozygotic (identical) pairs of twins aged 50-69 years, postmenopausal, and free of diseases affecting bone, recruited from a national register of twins and with a media campaign. Main outcome measures: Bone mineral density measured at the hip, lumbar spine, forearm, and for the whole body by dual energy x ray absorptiometry in relation to differences in the vitamin D receptor genotype. Results: At all sites the values of bone density among dizygotic twins were more similar in those of the same vitamin D receptor genotype than in those of differing genotype, and the values in the former were closer to the correlations seen in monozygotic twins. Women with the genotype that made them at risk of osteoporotic fracture had an adjusted bone mineral density that was significantly lower by SD 0.5 to 0.6 at the hip, lumbar spine, and for the whole body. The results could not be explained by differences in age, weight, years since menopause, or use of hormone replacement therapy. Conclusions: The findings that in postmenopausal women in Britain bone density—particularly at the hip and spine—is genetically linked and specifically associated with the vitamin D receptor genotypes should lead to novel approaches to the prevention and treatment of osteoporosis. Key messages Key messages Vitamin D has an important role in the metabolism of calcium and bone, mediated through its receptor Common variants of the vitamin D receptor gene are responsible for 7-10% of the difference in bone density between women after the menopause This genetic marker is important because of its potential role in identifying individual women at increased risk of fracture before menopause and in selecting optimal treatment