Incidence Of Nonvertebral Fractures Research Articles

Relation of alleles of the collagen type Ialpha1 gene to bone density and the risk of osteoporotic fractures in postmenopausal women.

Osteoporosis is a common disorder with a strong genetic component. One way in which the genetic component could be expressed is through polymorphism of COLIA1, the gene for collagen type Ialpha1, a bone-matrix protein. We determined the COLIA1 genotypes SS, Ss, and ss in a population-based sample of 1778 postmenopausal women using a polymerase-chain-reaction-based assay. We then related the genotypes to bone mineral density and the occurrence of osteoporotic fractures in these women. As compared with the 1194 women with the SS genotype, the 526 women with the Ss genotype had 2 percent lower bone mineral density at the femoral neck (P=0.003) and the lumbar spine (P=0.02); the 58 women with the ss genotype had reductions of 4 percent at the femoral neck (P= 0.05) and 6 percent at the lumbar spine (P=0.005). These differences increased with age (P=0.01 for modification by age of the effect of COLIA1 on femoral-neck bone density, and P=0.004 for modification of the effect on lumbar-spine bone density). Women with the Ss and ss genotypes were overrepresented among the 111 women who had incident nonvertebral fractures (relative risk per copy of the s allele, 1.5; 95 percent confidence interval, 1.1 to 2.1). The COLIA1 polymorphism is associated with reduced bone density and predisposes women to osteoporotic fractures.

Meta-analysis of Prevention of Nonvertebral Fractures by Alendronate

To the Editor. —As Dr Karpfand colleagues1demonstrate, alendronate use is associated with a reduced rate of nonvertebral osteoporotic fractures in selected populations. The relative risk and confidence intervals are impressive but are not adequate to formulate clinical decisions. Practicing clinicians should be hesitant to translate the study data directly to the prescription pad. The number needed to treat (NNT),2by its inverse relationship with absolute risk, has a much broader perspective on an intervention's effectiveness and provides an effort-yield ratio that a practicing clinician can use. It is a measure of how many people should receive an intervention to achieve the desired clinical end point in 1 person. From the alendronate data, the estimated cumulative incidence of nonvertebral fractures after 3 years was 12.6% in the control group and 9.0% in the alendronate group. From this the absolute risk reduction can be calculated to be 3.6%, and its inverse, the

Prevention of nonvertebral fractures by alendronate: A meta-analysis

Objective. —To evaluate the effect of treatment with alendronate sodium, a potent aminobisphosphonate, on the incidence of nonvertebral fractures in postmenopausal women with osteoporosis. Data Sources. —Published data and data on file at Merck Research Laboratories. Study Selection. —All completed prospective, randomized, placebo-controlled alendronate trials of at least 2 years' duration (5 studies). Data Extraction. —All subjects were women with osteoporosis between the ages of 42 and 85 years, postmenopausal at least 4years with lumbar spine bone mineral density (measured using dual-energy x-ray absorptiometry) at least 2.0 SD below the mean for young adult women. All women randomized to treatment with placebo or alendronate at a dose higher than 1 mg per day for at least 2 years were included. Data Synthesis. —In the placebo group (n=590), 60 women reported nonvertebral fractures during 1347 patient-years at risk (overall rate, 4.45 women with fractures per 100 patient-years at risk). In the alendronate group (n=1012), 73 women reported nonvertebral fractures during 2240 patient-years at risk (overall rate, 3.26 women with fractures per 100 patient-years at risk). The estimated cumulative incidence of nonvertebral fractures after 3 years was 12.6% in the placebo group and 9.0% in alendronate group. The relative risk for nonvertebral fracture estimated using the Cox proportional hazards model was 0.71 (95% confidence interval,0.502-0.997) (P=.048). A reduction in risk was consistent across each of the studies and at each major site of osteoporotic fracture, including the hip and wrist. Conclusion. —In postmenopausal women with osteoporosis, treatment with alendronate reduces the risk of nonvertebral fractures over at least 3 years.

Prevention of Nonvertebral Fractures by Alendronate

To evaluate the effect of treatment with alendronate sodium, a potent aminobisphosphonate, on the incidence of nonvertebral fractures in postmenopausal women with osteoporosis.Published data and data on file at Merck Research Laboratories.All completed prospective, randomized, placebo-controlled alendronate trials of at least 2 years' duration (5 studies).All subjects were women with osteoporosis between the ages of 42 and 85 years, postmenopausal at least 4 years, with lumbar spine bone mineral density (measured using dual-energy x-ray absorptiometry) at least 2.0 SD below the mean for young adult women. All women randomized to treatment with placebo or alendronate at a dose higher than 1 mg per day for at least 2 years were included.In the placebo group (n=590), 60 women reported nonvertebral fractures during 1347 patient-years at risk (overall rate, 4.45 women with fractures per 100 patient-years at risk). In the alendronate group (n = 1012), 73 women reported nonvertebral fractures during 2240 patient-years-at risk (overall rate, 3.26 women with fractures per 100 patient-years at risk). The estimated cumulative incidence of nonvertebral fractures after 3 years was 12.6% in the placebo group and 9.0% in alendronate group. The relative risk for nonvertebral fracture estimated using the Cox proportional hazards model was 0.71 (95% confidence interval,0.502-0.997) (P=.048). A reduction in risk was consistent across each of the studies and at each major site of osteoporotic fracture, including the hip and wrist.In postmenopausal women with osteoporosis, treatment with alendronate reduces the risk of nonvertebral fractures over at least 3 years.

Prevention of nonvertebral fractures by alendronate. A meta-analysis. Alendronate Osteoporosis Treatment Study Groups

To evaluate the effect of treatment with alendronate sodium, a potent aminobisphosphonate, on the incidence of nonvertebral fractures in postmenopausal women with osteoporosis. Published data and data on file at Merck Research Laboratories. All completed prospective, randomized, placebo-controlled alendronate trials of at least 2 years' duration (5 studies). All subjects were women with osteoporosis between the ages of 42 and 85 years, postmenopausal at least 4 years, with lumbar spine bone mineral density (measured using dual-energy x-ray absorptiometry) at least 2.0 SD below the mean for young adult women. All women randomized to treatment with placebo or alendronate at a dose higher than 1 mg per day for at least 2 years were included. In the placebo group (n=590), 60 women reported nonvertebral fractures during 1347 patient-years at risk (overall rate, 4.45 women with fractures per 100 patient-years at risk). In the alendronate group (n = 1012), 73 women reported nonvertebral fractures during 2240 patient-years-at risk (overall rate, 3.26 women with fractures per 100 patient-years at risk). The estimated cumulative incidence of nonvertebral fractures after 3 years was 12.6% in the placebo group and 9.0% in alendronate group. The relative risk for nonvertebral fracture estimated using the Cox proportional hazards model was 0.71 (95% confidence interval,0.502-0.997) (P=.048). A reduction in risk was consistent across each of the studies and at each major site of osteoporotic fracture, including the hip and wrist. In postmenopausal women with osteoporosis, treatment with alendronate reduces the risk of nonvertebral fractures over at least 3 years.

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 micro;g 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.

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.

Femoral trabecular-pattern index and bone mineral content measurement by photon absorption in senile osteoporosis

A comparative study of the usefulness of the femoral trabecular-pattern index (Singh index) and bone mineral content measurement by photon absorption in senile osteoporosis was performed in 106 white women, seventy to ninety-five years old. In 17% of the subjects adequate hip roentgenograms could not be obtained. Interpretation of the Singh index was not found to be simple and easily reproducible. A positive correlation was noted between the bone mineral content and the Singh index. The incidence of previous vertebral and non-vertebral fracture was noted to be inversely related to both bone mineral content and the Singh index, but neither method clearly separated subjects with fracture from those without fracture.