Bone density at various sites for prediction of hip fractures

Osteoporosis is a disorder in which loss of bone strength leads to fragility fractures. This review examines the fundamental pathogenetic mechanisms underlying this disorder, which include: (a) failure to achieve a skeleton of optimal strength during growth and development; (b) excessive bone resorption resulting in loss of bone mass and disruption of architecture; and (c) failure to replace lost bone due to defects in bone formation. Estrogen deficiency is known to play a critical role in the development of osteoporosis, while calcium and vitamin D deficiencies and secondary hyperparathyroidism also contribute. There are multiple mechanisms underlying the regulation of bone remodeling, and these involve not only the osteoblastic and osteoclastic cell lineages but also other marrow cells, in addition to the interaction of systemic hormones, local cytokines, growth factors, and transcription factors. Polymorphisms of a large number of genes have been associated with differences in bone mass and fragility. It is now possible to diagnose osteoporosis, assess fracture risk, and reduce that risk with antiresorptive or other available therapies. However, new and more effective approaches are likely to emerge from a better understanding of the regulators of bone cell function.

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Pathogenesis of osteoporosis: concepts, conflicts, and prospects

Data on the number of U.S. women with low femoral bone mineral density (BMD) are currently available only from indirect estimates. We used dual-energy X-ray absorptiometry (DXA) measurements of femoral BMD from phase 1 of the third National Health and Nutrition Examination Survey (NHANES III, 1988-1991) to estimate prevalences of low femoral BMD in women ages 50 years and older using an approach proposed recently by an expert panel of the World Health Organization (WHO). Cutpoints for low BMD were derived from BMD data of 194 non-Hispanic white (NHW) women aged 20-29 years from the NHANES III dataset. The prevalence of older U.S. women with femoral osteopenia (BMD between 1 standard deviation [SD] and 2.5 SD below the mean of young NHW women) ranged from 34-50% in four different femur regions, which corresponds to approximately 12-17 million women. The prevalence with osteoporosis (BMD > 2.5 SD below the mean of young NHW women) ranged from 17-20%, or approximately 6-7 million women. Prevalences were 1.3-2.4 times higher in NHW women than non-Hispanic black women (NHB), and 0.8-1.2 times higher in NHW versus Mexican American (MA) women. The estimated numbers of NHW, NHB, and MA women with osteopenia were 10-15 million, 800,000-1.2 million, and 300,000-400,000, respectively; corresponding figures for osteoporosis were 5-6 million, 200,000-300,000, and 100,000 respectively. Thus, the first data on BMD from a nationally representative sample of older women show a substantial number with low femoral BMD.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of low femoral bone density in older U.S. adults from NHANES III.

The worldwide problem of osteoporosis: insights afforded by epidemiology.

Osteoporosis is widely viewed as a major public health concern, but the exact magnitude of the problem is uncertain and likely to depend on how the condition is defined. Noninvasive bone mineral measurements can be used to define a state of heightened fracture risk (osteopenia), or the ultimate clinical manifestation of fracture can be assessed (established osteoporosis). If bone mineral measurements more than 2 standard deviations below the mean of young normal women represent osteopenia, then 45% of white women aged 50 years and over have the condition at one or more sites in the hip, spine, or forearm on the basis of population-based data from Rochester, Minnesota. A smaller proportion is affected at each specific skeletal site: 32% have bone mineral values this low in the lumbar spine, 29% in either of two regions in the proximal femur, and 26% in the midradius. Although this overall estimate is substantial, some other serious chronic diseases are almost as common. More importantly, low bone mass is associated with adverse health outcomes, especially fractures. The lifetime risk of any fracture of the hip, spine, or distal forearm is almost 40% in white women and 13% in white men from age 50 years onward. If the enormous costs associated with these fractures are to be reduced, increased attention must be given to the design and implementation of control programs directed at this major health problem.

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Perspective : how many women have osteoporosis ?

Patterns of bone loss in the axial and the appendicular skeleton were studied in 185 normal volunteers (105 women and 82 men; age range, 20--89 yr) and in 76 women and 9 men with vertebral fractures due to osteoporosis. Bone mineral density was measured in vivo at the lumbar spine (predominantly trabecular bone) by dual photon absorptiometry and at the midradius (greater than 95% cortical bone) and distal radius (75% cortical and 25% trabecular bone) by single photon absorptiometry. In normal women, bone diminution from the vertebrae began in young adulthood and was linear. In the appendicular skeleton, bone diminution did not occur until age 50 yr, was accelerated from aged 51 to 65 yr, and then decelerated somewhat after age 65 yr. Overall bone diminution throughout life was 47% for the vertebrae, 30% for the midradius, and 39% for the distal radius. In normal men, vertebral and appendicular bone diminution with aging was minimal or insignificant. Mean bone mineral density was lower in patients with osteoporosis than in age- and sex-matched normal subjects at all three scanning sites, although spinal measurements discriminated best; however, there was considerable overlap. By age 65 yr, half of the normal women (and by age 85 yr, virtually all of them) had vertebral bone mineral density values below the 90th percentile of women with vertebral fractures and, thus, might be considered to have asymptomatic osteoporosis. For men, the degree of overlap was less. The data suggest that disproportionate loss of trabecular bone from the axial skeleton is a distinguishing characteristic of spinal osteoporosis.

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Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis.

We measured bone mineral density (BMD) of the proximal femur, lumbar spine, or both by dual photon absorptiometry in 205 normal volunteers (123 women and 82 men; age range 20 to 92 yr) and in 31 patients with hip fractures (26 women and 5 men; mean age, 78 yr). For normal women, the regression of BMD on age was negative and linear at each site; overall decrease during life was 58% in the femoral neck, 53% in the intertrochanteric region of the femur, and 42% in the lumbar spine. For normal men, the age regression was linear also; the rate of decrease in BMD was two-thirds of that in women for femoral neck and intertrochanteric femur but was only one-fourth of that in women for lumbar spine. This difference may explain why the female/male ratio is 2:1 for hip fractures but 8:1 for vertebral fractures. The standard deviation (Z-score) from the sex-specific age-adjusted normal mean in 26 women with hip fracture averaged -0.31 (P < 0.05) for the femoral neck, -0.53 (P < 0.01) for the intertrochanteric femur, and +0.24 (NS) for the lumbar spine; results were similar for 5 men with hip fractures. By contrast, for 27 additional women, ages 51-65 yr, with only nontraumatic vertebral fractures, the Z-score was -1.92 (P < 0.001) for the lumbar spine. Thus, contrary to the view that osteoporosis is a single age-related entity, our data suggest the existence of two distinct syndromes. One form, "postmenopausal osteoporosis," is characterized by excessive and disproportionate trabecular bone loss, involves a small subset of women in the early postmenopausal period, and is associated mainly with vertebral fractures. The other form, "senile osteoporosis," is characterized by proportionate loss of both cortical and trabecular bone, involves essentially the entire population of aging women and, to a lesser extent, aging men, and is associated with hip fractures or vertebral fractures or both.

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Changes in Bone Mineral Density of the Proximal Femur and Spine with Aging: DIFFERENCES BETWEEN THE POSTMENOPAUSAL AND SENILE OSTEOPOROSIS SYNDROMES

Dual-photon absorptiometry with gadolinium 153 was used to measure the mineral content of lumbar vertebrae in cadavers, excised vertebrae with marrow, and dry, marrow-free vertebrae. The error introduced by the surrounding soft tissue of cadavers was 3%, and the error in determining mineral mass or density in excised vertebrae was about 5%. The correlation coefficient between the results of Gd-153 and corrected iodine 125 (single-photon) absorptiometry on 24 femoral necks was 0.99, and the predictive error was 3.7%. Dual-photon absorptiometry accurately indicates bone mass and bone density and is only slightly affected by either surrounding tissue or fat changes in bone marrow.

Dual-photon Gd-153 absorptiometry of bone.

We measured bonemineral density (BMD)oftheproximal femur, lumbar spine, orboth bydualphoton absorptiometry in205normal volun- teers (123 womenand82men;agerange 20to92yr) andin31patients withhipfractures (26womenand 5 men;meanage,78yr). Fornormal women,the regression ofBMD onagewasnegative andlinear at eachsite; overall decrease during life was58%inthe femoral neck, 53%intheintertrochanteri c

Changes inBoneMineral Density oftheProximal Femur andSpine withAging DIFFERENCES BETWEEN THE POSTMENOPAUSAL AND SENILE OSTEOPOROSIS SYNDROMES

Patterns ofboneloss intheaxial andthe appendicular skeleton werestudied in187normal volunteers (105womenand82men;agerange, 20- 89yr)andin76womenand9menwithvertebral fractures duetoosteoporosis. Bonemineral density wasmeasured invivoatthelumbarspine(pre- dominantly trabecular bone) bydualphoton absorp- tiometry andatthemidradius (>95%cortical bone) and distal radius (75%cortical and25%trabecular bone) bysingle photon absorptiometry. Innormal women, bonediminution fromthevertebrae beganinyoung adulthood andwaslinear. Intheappendicular skeleton, bonediminution didnotoccuruntil age50yr,was accelerated fromages51to65yr,andthendecelerated somewhat after age65yr.Overall bonediminution throughout life was47%forthevertebrae, 30%for themidradius, and39%for thedistal radius. Innormal men,vertebral andappendicular bonediminution with aging wasminimal orinsignificant. Meanbonemineral density waslower inpatients withosteoporosis than inage-andsex-matched normal subjects atallthree scanning sites, although spinal measurements dis- criminated best; however, there wasconsiderable over- lap. Byage65yr,half ofthenormal women(and byage 85yr,virtually allofthem) hadvertebral bonemineral density values belowthe90thpercentile ofwomen withvertebral fractures and, thus, might beconsidered tohaveasymptomatic osteoporosis. Formen,the degree ofoverlap wasless. Thedatasuggest that disproportionate loss oftrabecular bonefromtheaxial skeleton isadistinguishing characteristic ofspinal osteoporosis.

R. B. Mazess

Papers

Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis.

Changes in Bone Mineral Density of the Proximal Femur and Spine with Aging: DIFFERENCES BETWEEN THE POSTMENOPAUSAL AND SENILE OSTEOPOROSIS SYNDROMES

Dual-photon Gd-153 absorptiometry of bone.

Changes inBoneMineral Density oftheProximal Femur andSpine withAging DIFFERENCES BETWEEN THE POSTMENOPAUSAL AND SENILE OSTEOPOROSIS SYNDROMES

Differential Changes inBoneMineral Density of theAppendicular andAxial Skeleton withAging