Showing papers in "Osteoporosis International in 1997"
TL;DR: It is concluded that the socioeconomic impact of hip fractures will increase markedly throughout the world, particularly in Asia, and that there is an urgent need to develop preventive strategies,particularly in the developing countries.
Abstract: The aims of this study were to estimate the present and future incidence of hip fracture world-wide. From a survey of available data on current incidence, population trends and the secular changes in hip fracture risk, the numbers of hip fractures expected in 2025 and 2050 were computed. The total number of hip fractures in men and women in 1990 was estimated to be 338000 and 917000 respectively, a total of 1.26 million. Assuming no change in the age- and sex-specific incidence, the number of hip fractures is estimated to approximately double to 2.6 million by the year 2025, and 4.5 million by the year 2050. The percentage increase will be greater in men (310%) than in women (240%). With modest assumptions concerning secular trends, the number of hip fractures could range between 7.3 and 21.3 million by 2050. The major demographic changes will occur in Asia. In 1990, 26% of all hip fractures occurred in Asia, whereas this figure could rise to 37% in 2025 and to 45% in 2050. We conclude that the socioeconomic impact of hip fractures will increase markedly throughout the world, particularly in Asia, and that there is an urgent need to develop preventive strategies, particularly in the developing countries.
1,932 citations
TL;DR: The results showed that in French normal adults living in an urban environment with a lack of direct exposure to sunshine, diet failed to provide an adequate amount of vitamin D, and the clinical utility of winter supplementation with low doses ofitamin D was discussed.
Abstract: The vitamin D status of a general adult urban population was estimated between November and April in 1569 subjects selected from 20 French cities grouped in nine geographical regions (between latitude 43° and 51° N). Major differences in 25-hydroxyvitamin D (25(OH)D) concentration were found between regions, the lowest values being seen in the North and the greatest in the South, with a significant ‘sun’ effect (r = 0.72; p = 0.03) and latitude effect (r = -0.79; p = 0.01). In this healthy adult population, 14% of subjects exhibited 25(OH)D values ≤ 30 nmol/l (12 ng/ml), which represents the lower limit (< 2 SD) for a normal adult population measured in winter with the same method (RIA Incstar). A significant negative correlation was found between serum intact parathyroid hormone (iPTH) and serum 25(OH)D values (p < 0.01). Serum iPTH held a stable plateau level at 36 pg/ml as long as serum 25(OH)D values were higher than 78 nmol/l (31 ng/ml), but increased when the serum 25(OH)D value fell below this. When the 25(OH)D concentration became equal to or lower than 11.3 nmol/l (4.6 ng/ml), the PTH values reached the upper limit of normal values (55 pg/ml) found in vitamin D replete subjects. These results showed that in French normal adults living in an urban environment with a lack of direct exposure to sunshine, diet failed to provide an adequate amount of vitamin D. It is important to pay attention to this rather high prevalence of vitamin D insufficiency in the general adult population and to discuss the clinical utility of winter supplementation with low doses of vitamin D.
1,475 citations
TL;DR: A need to develop practice guidelines for primary care physicians is recognized, which recognize the multifactorial nature of the events which give rise to the fractures, but operational definitions have now been agreed and have gained a wide measure of acceptance.
Abstract: Significant developments have occurred in the field of osteoporosis over the past several years. There is now considerable information concerning its impact on general health and an international consensus concerning the definition of osteoporosis. Conceptually, this recognizes the multifactorial nature of the events which give rise to the fractures, but operational definitions have now been agreed and have gained a wide measure of acceptance. Accurate and precise diagnostic tools are also available. Finally, there is substantial evidence that the natural history of osteoporosis can be modulated by agents which in turn decrease the risk of fracture. Despite an increasing professional and public awareness of osteoporosis, the management of osteoporosis has been confined mainly to specialists. With the large number of affected individuals and the wider availability of diagnostic aids and safe treatments, there is a need for osteoporosis to be managed predominantly by the primary care physician. Against this background the European Foundation for Osteoporosis and Bone Disease through their Scientific Advisory Board has recognized a need to develop practice guidelines for primary care physicians which are summarized in this paper.
753 citations
TL;DR: Quantitative ultrasound (QUS) measurement [broadband ultrasound attenuation (BUA) and velocity] is emerging as an alternative to photon absorptiometry techniques in the assessment of osteoporosis and the fundamental principles governing ultrasound measurements are discussed.
Abstract: Osteoporosis is now being recognized as a "silent epidemic" and there is an increasing need to improve its diagnosis and management. Quantitative ultrasound (QUS) measurement [broadband ultrasound attenuation (BUA) and velocity] is emerging as an alternative to photon absorptiometry techniques in the assessment of osteoporosis. The fundamental principles governing ultrasound measurements are discussed, and some of the commercially available clinical systems are reviewed, particularly in relation to data acquisition methods. A review of the published in vivo and in vitro data is presented. The general consensus is that ultrasound seems to provide structural information in addition to density. The diagnostic sensitivity of ultrasound measurement of the calcaneus in the prediction of hip fracture has been shown by recent large prospective studies to be similar to hip bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) and superior to spine BMD. Ultrasound has also been shown to correlate better with the type of hip fracture (intertrochanteric or cervical) than BMD and to provide comparable diagnostic sensitivity to spine BMD in vertebral fractures. It has also been observed that combining the results of both ultrasound and DXA BMD significantly improved hip fracture prediction. Areas where further research is required are identified.
555 citations
TL;DR: Lumbar spine ostoephytes affect most subjects over the age of 60 years, and contribute substantially to lumbar spinal BMD measured in the anteroposterior position by DXA, which is largely direct by virtue of osteophytes being included in the BMD measurement.
Abstract: To determine in the elderly the effect of osteoarthritis on bone mineral density (BMD) and on diagnosis of osteoporosis, lumbar spine and hip were radiographed and BMD measured by dual-energy X-ray absorptiometry (DXA) in 120 men and 314 women, aged 60–99 years. Prevalence and severity of osteoarthritis were scored on osteophytes, joint space narrowing and bone sclerosis. Ultrasound measurements were also made at the heel to examine whether osteoarthritis at hip or lumbar spine influence bone at this remote site. Osteophytes were the commonest feature, with men having a higher prevalence than women, and lumbar spine having more disease than hip. Lumbar spine osteophytes affected 75% of men and 61.1% of women, and hip osteophytes affected 31.7% of men and 27.4% of women. Stepwise multiple regression analysis using age, weight, height, osteophytes, sclerosis and joint space narrowing indicated that lumbar osteophytes explained 16.6% of variation in lumbar spine BMD in women, and 22.4% in men. Hip osteophytes had a minimal effect on hip BMD, accounting for only 2.2% of variation in women, and none in men. Sclerosis and joint narrowing had little effect on BMD at lumbar spine or hip. Indirect effects of osteoarthritis on BMD were small and inconsistent across genders. Lumbar spine osteophytes in men explained 3.1% of hip BMD variation and 6% of variation in speed of sound at the heel, whereas hip osteophytes in women explained 2.2% of lumbar spine BMD variation. Osteoporosis at the hip, defined as BMD <2.5 SD of the young normal mean, was present in 33.1% of women and 25.8% of men, whereas, at the lumbar spine it was present in only 24.2% of women and 4.2% of men. However, in women and men free of spinal osteoarthritis, 37.7% of women and 10% of men had osteoporosis. We conclude that lumbar spine ostoephytes affect most subjects over the age of 60 years, and contribute substantially to lumbar spine BMD measured in the anteroposterior position by DXA. The effect is largely direct by virtue of osteophytes being included in the BMD measurement. However, a small indirect effect on remote skeletal sites is also present. Diagnosis of osteoporosis and assessment of osteoporotic fracture risk in the elderly should be based on hip BMD and not on anteroposterior lumbar spine, unless spinal osteoarthritis has been excluded.
262 citations
TL;DR: This meta-analysis suggests that exercise programs in a population of postmenopausal women over 50 years of age are effective for preventing spinal bone mineral density loss at the L2–4 level, however, such programs do not have any effect on the forearm or femoral bone mass.
Abstract: A meta-analysis was done to measure the effect of physical activity on the bone mass of healthy postmenopausal women All studies published between 1966 and 1996, in French or English, were reviewed for inclusion from Medline search, bibliographies of relevant studies, review articles and books Studies had to be prospective intervention trials, randomized or not, evaluating the effectiveness of an exercise program of any duration, frequency and intensity, with a control group Studies had to measure bone parameters and involve healthy postmenopausal women over 50 years of age who were free of symptomatic osteoporosis at the time of study entry Effect sizes (ES) were calculated for each bone parameter and site measured in every eligible study according to Hedges and Olkin DerSimonian and Laird's model was used to estimate overall effect sizes when combining studies All analyses were bone parameter and site specific Of 217 papers extracted from the literature, 187 did not meet eligibility criteria and 12 others were rejected The two main reasons for rejection were that both genders were combined in the analyses and no exercise group without drug interaction was present Eighteen studies were included for meta-analysis Taking into account the frequency, duration, compliance rate and average age of the subjects, the programs were judged of moderate intensity and focused on walking, running, physical conditioning and aerobics A significant effect of physical activity was detected on the bone mineral density at the L2-4 level of the lumbar column in studies published after 1991 (ES = 08745, p < 005) No effect could be seen, however, on forearm and femoral bone mass Although applied to a small number of studies, this meta-analysis suggests that exercise programs in a population of postmenopausal women over 50 years of age are effective for preventing spinal bone mineral density loss at the L2-4 level However, such programs do not have any effect on the forearm or femoral bone mass
249 citations
TL;DR: Although only moderately correlated with BMD, QUS appears to be as strong a predictor of osteoporotic fracture as BMD and may predict fracture independent of BMD.
Abstract: Quantitative ultrasound (QUS) is a simple, inexpensive and non-invasive measure of bone which has been used in research settings for the prediction of osteoporosis. This review summarizes the current status of the epidemiology of QUS analysis, including its relationship with bone mineral density (BMD), risk of osteoporotic fracture and risk factors for osteoporosis. Although only moderately correlated with BMD, QUS appears to be as strong a predictor of osteoporotic fracture as BMD and may predict fracture independent of BMD. Risk factors for low QUS, including age, menopause, body composition and physical inactivity, seem to parallel those of low BMD. More longitudinal research is needed to confirm the clinical utility of QUS and more experimental and population-based studies are needed to determine whether the etiology of low QUS values is different from that of low bone mass.
245 citations
TL;DR: Values for femoral neck BMD in the female population become statistically lower after the age of 49 years, while in the male population this effect was seen after the Age of 69 years, and values for lumbar spine BMD were higher in men than women at all ages.
Abstract: The aim of this study was to generate standard curves for bone mineral density (BMD) in a Spanish population using dual-energy X-ray absorptiometry (DXA), at both lumbar spine and femoral neck sites. The total sample size was 2442 subjects of both sexes aged 20-80 years, stratified according to survival rates, demographic distribution by local regions and sex ratio in the Spanish population. Subjects with suspected conditions affecting bone metabolism or receiving any treatment affecting bone mineralization were excluded. The study was carried out in 14 hospitals and bone density measurements were performed, using a QDR/ 1000 Hologic device. In the female population, the highest value for lumbar spine BMD was found within the 30-39 years age group, being significantly lower after the age of 49 years. In the male population, the highest values for lumbar spine BMD are found one decade earlier than in the female population and become significantly lower after the age of 69 years. The highest values for femoral neck BMD in men and women was found in the 20-29 year age group. Values for femoral neck BMD in the female population become statistically lower after the age of 49 years, while in the male population this effect was seen after the age of 69 years. Values for femoral neck BMD were higher in men than women at all ages.
180 citations
TL;DR: There are major differences between BMD values in European population samples which, with variations in anthro-pometric variables, have the potential to contribute substantially to variations in rates of osteoporotic fracture risk in Europe.
Abstract: The purpose of this study was to investigate variations in bone density between 16 European populations, 13 of which were participants in the European Vertebral Osteoporosis Study (EVOS). Men and women aged 50–80 years were recruited randomly from local population registers, stratified in 5-year age bands. The other three centres recruited similarly. Random samples of 20–100% of EVOS subjects were invited for dual-energy X-ray absorptiometry (DXA) densitometry of the lumbar spine and/or proximal femur using Hologic, Lunar or Norland pencil beam machines or, in one centre, a Sopha fan-beam machine. Cross-calibration of the different machines was undertaken using the European Spine Phantom prototype (ESPp). Highly significant differences in mean bone density were demonstrated between centres, giving rise to between-centre SDs in bone density that were about a quarter of a population SD. These differences persisted when centres using Hologic machines and centres using Lunar machines were considered separately. The centres were ranked differently according to whether male or female subjects were being considered and according to site of measurement (L2–4, femoral neck or femoral trochanter). As expected, bone mineral density (BMD) had a curvilinear relationship with age, and apparent rates of decrease slowed as age advanced past 50 years in both sexes. In the spine, not only did male BMD usually appear to increase with age, but there was a highly significant difference between centres in the age effect in both sexes, suggesting a variability in the impact of osteoarthritis between centres. Weight was consistently positively associated with BMD, but the effects of height and armspan were less consistent. Logarithmic transformation was needed to normalize the regressions of BMD on the independent variates, and after transformation, all sites except the femoral neck in females showed significant increases in SD with age. Interestingly, the effect of increasing weight was to decrease dispersion in proximal femur measurements in both sexes, further accentuating the tendency in women for low body mass index to be associated with osteoporosis as defined by densitometry. It is concluded that there are major differences between BMD values in European population samples which, with variations in anthro-pometric variables, have the potential to contribute substantially to variations in rates of osteoporotic fracture risk in Europe.
164 citations
TL;DR: There is enough economic evidence to justify wide-scale interventions against osteoporosis in Switzerland, and days of hospital stay caused by chronic obstructive pulmonary disease, stroke, acute myocardial infarction and breast cancer were estimated using the same methodology.
Abstract: The objective of this study was to estimate the annual direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland. Days of hospital stay in 1992 were quantified using the casuistic of the medical statistics department of VESKA (Vereinigung Schweizerischer Krankenhauser, the Swiss Hospital Association), which covers 43% of all hospital beds of that country. Number and incidence of total hospitalizations due to fractures were calculated by extrapolating to 100% the 43% VESKA-selected sample. To estimate number and incidence of hospitalizations due to osteoporotic fractures, internationally accepted age-specific osteoporosis attribution rates were applied. According to the latter the probability of a fracture being caused by osteoporosis increases with age. Mean length of stay for all fractures was calculated (= total hospital days divided by number of cases). By multiplying these mean lengths of stay by the number of osteoporosis-related fracture cases, the number of bed-days due to osteoporotic fractures was calculated. To compare the direct medical costs of hospitalization due to osteoporosis with those due to other frequent diseases, days of hospital stay caused by chronic obstructive pulmonary disease (COPD), stroke, acute myocardial infarction and breast cancer were estimated using the same methodology. A total estimate of 63,170 (f: 33,596, m: 29,574) hospitalizations due to fractures (and other osteoporosis-related diagnoses) was calculated, thus leading to overall annual incidence rates of hospitalizations for fractures of 950/100,000 women and 877/100,000 men. In women, 548,615 hospital days were found to be caused by osteoporosis, 353,654 days by COPD, 352,062 days by stroke, 200,669 days by breast carcinoma and 131,331 days by myocardial infarction. In men, COPD caused more hospitalization days (537,164) than myocardial infarction (196,793), stroke (180,524) or osteoporosis (152,857). Taking a mean price for a hospital day in Switzerland of 845 Swiss francs, the annual costs of acute hospitalizations due to osteoporosis and its complications were approximately 600 million Swiss francs (f: 464, m: 130 million Swiss francs) in 1992. We conclude that there is enough economic evidence to justify wide-scale interventions against osteoporosis in Switzerland.
154 citations
TL;DR: An increase in BMD at the spine with calcium supplementation in females with a mean age of 14 years is found, and the continuance of the intervention until the attainment of peak bone mass and follow-up after cessation of calcium supplementation will be important in clarifying the optimal timing for increased dietary calcium and the sustained, long-term effects of this intervention.
Abstract: The effect of calcium supplementation on bone mineral density (BMD) was evaluated in female twin pairs aged 10-17 years with a mean age of 14 years. Forty-two twin pairs (22 monozygotic, 20 dizygotic; (including one monozygotic pair from a set of triplets) completed at least 6 months of the intervention: 37 pairs to 12 months and 28 pairs to 18 months. BMD was measured by dual-energy X-ray absorptiometry (DXA). In a double-blind manner, one twin in each pair was randomly assigned to receive daily a 1000 mg effervescent calcium tablet (Sandocal 1000), and the other a placebo tablet similar in taste and appearance to the calcium supplement but containing no calcium. Compliance (at least 80% tablets consumed), as measured by tablet count, was 85% in the placebo group and 83% in the calcium group over the 18 months of the study, on average increasing dietary calcium to over 1600 mg/day. There was no within-pair difference in the change in height or weight. When the effect of calcium supplementation on BMD was compared with placebo at approximately 6, 12 and 18 months, it was found that there was a 0.015 +/- 0.007 g/ cm2 greater increase in BMD (1.62 +/- 0.84%) at the spine in those on calcium after 18 months. At the end of the first 6 months there was a significant within-pair difference of 1.53 +/- 0.56% at the spine and 1.27 +/- 0.50% at the hip. However, there were no significant differences in the changes in BMD after the initial effect over the first 6 months. Therefore, we found an increase in BMD at the spine with calcium supplementation in females with a mean age of 14 years. The greatest effect was seen in the first 6 months; thereafter the difference was maintained, but there was no accelerated increase in BMD associated with calcium supplementation. The continuance of the intervention until the attainment of peak bone mass and follow-up after cessation of calcium supplementation will be important in clarifying the optimal timing for increased dietary calcium and the sustained, long-term effects of this intervention.
TL;DR: The results suggest early intervention is necessary to prevent irreversible vertebral bone loss in oligo/amenorrheic athletes and indicates the need to select athletes suitable for vaginal or laparoscopic mesh placement for mesh placement after menses.
Abstract: Small gains in bone mineral density (BMD) have been reported in the first year following resumption of menses in amenorrheic athletes but there have been no long-term outcome studies. The purpose of this study was to determine whether the BMD of former oligomenorrheic or amenorrheic athletes normalizes following several years of normal menses or use of oral contraceptives. Twenty-nine athletes first studied in this laboratory 8.1 years (range 6-10 years) ago were available for follow-up. At recruitment (time 1) 29 athletes, mean age of 30.6 years, were non-smokers, exercised 4 or more days/week for at least 45 min, had not used oral contraceptives, and had no medical conditions affecting bone metabolism. At time 1, 9 women (R/R) had always menstruated regularly, 9 (R/O/A) had experienced intermittent oligo/amenorrhea as well as regular menses, and 11 (O/A) had never menstruated regularly. At follow-up (time 2) mean age of the women was 38.2 years and there were no significant changes in height, weight or activity patterns. BMD (g/cm2) was measured at the lumbar vertebrae (L1-4 and femoral neck by dual-energy X-ray absorptiometry and expressed as a percentage of R/R values. Vertebral BMD was significantly lower in the O/A group compared with the R/R group at both time 1 and time 2 (p < 0.05). The R/O/A group had intermediate values and did not differ significantly from R/R or O/A at either time. Differences in technique between machines for determining femoral neck BMD made it difficult to detect the longitudinal effect of menstrual status at that site. Despite several years of normal menses or use of oral contraceptives, the mean vertebral BMD of former oligo-amenorrheic athletes remained low, being 84.4% of the R/R value compared to 84.8% at time 1. Those experiencing menstrual regularity with intermittent oligo/amenorrhea remained at an intermediate position of 94.7% of the R/R mean. Our results suggest early intervention is necessary to prevent irreversible vertebral bone loss in oligo/amenorrheic athletes.
TL;DR: Preliminary results indicate that the reproducibility is sufficient and that the questionnaire is able to discriminate between patients with vertebral osteoporosis and control subjects.
Abstract: The morbidity of osteoporosis is caused by fractures. Vertebral fractures lead to pain and disability and a decrease in quality of life. A Working Party of the European Foundation for Osteoporosis has developed a specific questionnaire for patients with established vertebral osteoporosis. This questionnaire is intended for use in clinical trials. The questionnaire consists of questions and visual analogue scales in the following domains: pain, activities of daily living, jobs around the house, mobility, leisure and social activities, general health perception and mood. The questionnaire has been translated from English into French, German, Italian, Hebrew, Swedish and Dutch. The questionnaire is currently being validated in a multicentre study involving patients with stable osteoporosis and control subjects. Preliminary results indicate that the reproducibility is sufficient and that the questionnaire is able to discriminate between patients with vertebral osteoporosis and control subjects.
TL;DR: Recent progress is presented in the understanding of the role of vitamin D and PTH in bone and calcium homeostasis, advances in diagnostic tools and therapeutic agents, and epidemiology was an important topic.
Abstract: Primary osteoporosis is a worldwide problem in elderly individuals. In ‘Osteoporosis Update 1997’ there are many outstanding contributions from all over the world. Recent progress is presented in the understanding of the role of vitamin D and PTH in bone and calcium homeostasis, advances in diagnostic tools and therapeutic agents. Since one of the aims of the Second International Conference on Osteoporosis was to compare risk factors among different nations, epidemiology was an important topic. p] Another feature of interest was that bone and calcium abnormalities are not only the problem of bone and calcium per se, but are also related to abnormalities in many other disorders such as atherosclerosis and cancer. Regarding atherosclerosis, bone-vascular system correlation may be a problem of interest to study in the future.
TL;DR: A dissociation between the rates of statural growth and mineral mass accrual could define a state of relatively low bone mass and contribute to the higher incidence of fracture known to occur at the age and/or pubertal stage when this dissociation is maximal.
Abstract: During puberty, the marked increases in both standing height and bone mass appear to be dissociated in time, the former occurring earlier than the latter. However, the age or pubertal stage at which this dissociation is maximal in girls as opposed to boys, and whether this dissociation is similar at all parts of the skeleton, are not clearly established. Standing height and bone mineral mass, as assessed by measuring areal bone mineral density (BMD), at the levels of the lumbar spine, femoral neck and midfemoral shaft, were measured in 98 females and 100 males between the ages of 9 and 19 years twice at a 1-year interval. In males, the greatest difference between height and BMD gains occurred in the 13–14 year age group and was more pronounced for the lumbar spine and femoral neck than for the midfemoral shaft. In females, the greatest difference was detectable at a younger age (11–12 year age group) and appeared to be of a lower magnitude than in males. In both genders, the maximal difference occurred during the period of peak height velocity, which corresponded to the pubertal stages P2-P3. Such a dissociation between the rates of statural growth and mineral mass accrual could define a state of relatively low bone mass and contribute to the higher incidence of fracture known to occur at the age and/or pubertal stage when this dissociation is maximal.
TL;DR: Serum TRAP activity is confirmed as a valid cytochemical marker for identification of osteoclasts, but is an osteoclastic marker of weak sensitivity due to known factors, such as synthesis of the enzyme not being unique to osteoclast, enzyme instability, and the presence of inhibitors in serum.
Abstract: Tartrate-resistant acid phosphatase (TRAP) activity is regarded as an important cytochemical marker of osteoclasts; its concentration in serum is utilized as a biochemical marker of osteoclast function and degree of bone resorption. This study was carried out to assess the sensitivity of TRAP activity both as a cytochemical marker in histological sections and as a biochemical marker in serum in comparison with the standardized histomorphometric variables of osteoclasts. To this end we investigated 24 patients (21 women, 3 men; 60 +/- 17 years of age) affected with various metabolic bone diseases. Osteoclast surface (OcS/BS) and osteoclast number (OcN/BS) were evaluated by standardized histomorphometry in iliac crest biopsies. On the basis of TRAP cytochemical activity, TRAP-positive osteoclast surface (TRAP + OcS/BS) and number (TRAP + OcN/BS) were measured. TRAP-positive cells adjacent to bone and showing one nucleus or no nuclei at all in the plane of section were included in the counts as osteoclasts. Serum TRAP activity was determined by spectrophotometric assay. Values of OcS/BS and OcN/BS were much lower than those of TRAP + OcS/BS (-50%) and TRAP + OcN/BS (-60%), respectively. Correlations between OcS/BS and TRAP + OcS/BS, and between OcN/BS and TRAP + OcN/BS, were highly significant. Serum TRAP was significantly correlated with OcS/BS, OcN/BS, and TRAP + OcN/BS. These correlations, however, were rather low. Moreover, serum TRAP did not correlate with TRAP + OcS/BS. From these results, the conclusion can be drawn that while TRAP activity is confirmed as a valid cytochemical marker for identification of osteoclasts, serum TRAP activity is an osteoclastic marker of weak sensitivity. This may be due to known factors, such as synthesis of the enzyme not being unique to osteoclasts, enzyme instability, and the presence of inhibitors in serum. Mononucleated osteoclasts do not significantly influence the serum enzyme levels.
TL;DR: The ability of quantitative ultrasound and bone mineral density to predict stiffness and strength of human femoral heads removed from live subjects during hip replacement was assessed and suggests that BMD measured using DXA, if used in conjunction with ultrasound velocity, may be able to improve osteoporosis risk assessment.
Abstract: The stiffness and strength of cancellous bone are important in the management of skeletal diseases such as osteoporosis. These properties are a function not only of bone density but also of bone architecture, some measure of which can be provided by quantitative ultrasound. The ability of quantitative ultrasound and bone mineral density (BMD) to predict stiffness and strength of human femoral heads removed from live subjects during hip replacement was assessed. Stiffness and strength were measured using a uniaxial compression test. Ultrasound velocity was measured using the pulse-submersion technique (McClue CUBAResearch) and BMD using DXA (Lunar DPX-L). Ultrasound velocity (quantitative ultrasound) and stiffness varied with the three orthogonal directions, the highest significance being between the proximo-distal (PD) and antero-posterior (AP) directions (p < 0.0001) for stiffness and p = 0.0003 for velocity). Ultrasound velocity was significantly correlated with compressive bone strength (r = 0.76, p < 0.0001) and stiffness (r = 0.79–0.83, p < 0.0001). BMD was also significantly correlated with compressive strength (r = 0.82, p < 0.0001) and stiffness (r = 0.66–0.81, p < 0.001). Using multiple regression analysis both BMD and velocity were significant predictors of strength (r = 0.88, p = 0.0004 and 0.0054 respectively) and stiffness r = 0.92, p = 0.0001 and 0.0003 respectively). BMD and velocity were still independent significant predictors of both stiffness (r = 0.93, p < 0.0001 and 0.0001 respectively) and strength (r = 0.89, p < 0.0001 and 0.02) when they combined as a product (BMDn*Vm). This suggests that BMD measured using DXA, if used in conjunction with ultrasound velocity, may be able to improve osteoporosis risk assessment. The information about femur anisotropy may also be important for hip prosthesis and in vivo modelling.
TL;DR: It is demonstrated for the first time that human osteoblasts, like several other diploid cell types, have a limited proliferative capacity in vitro and undergo aging and senescence as measured by various cellular and biochemical markers.
Abstract: The proliferative capacity and cellular and biochemical characteristics of human trabecular bone osteoblasts were analysed throughout their replicative lifespan in vitro. Like several other cell types, human osteoblasts demonstrated a typical Hayflick phenomenon of cellular aging comprising a period of rapid proliferation until cumulative population doubling level (CPDL) 22 to 24, followed by a phase of slow growth and the final cessation of cell division at CPDL 32 to 34. Comparing young cells (less than 20% lifespan completed) and old cells (more than 90% lifespan completed) revealed a progressive increase in population doubling (PD) time, a decrease in attachment frequency, a decrease in the number of S-phase positive cells, a decrease in the rates of DNA, RNA and protein synthesis, an increase in the protein content per cell and an increased proportion of senescence-specificβ-galactosidase positive cells. While osteoblastic production of collagen type I decreased progressively during aging, alkaline phosphatase activity dropped rapidly after the first few passages and then remained constant during the rest of the proliferative lifespan. Significant morphological changes from thin and spindle-shaped early passage young cells to large, flattened and irregularly shaped late passage old cells full of intracellular debris were observed. In comparison, osteoblasts established from an osteoporotic bone sample showed a maximum CPDL of less than 5, had a longer PD time and exhibited abnormal senescent morphology. Thus, we have demonstrated for the first time that human osteoblasts, like several other diploid cell types, have a limited proliferative capacity in vitro and undergo aging and senescence as measured by various cellular and biochemical markers. In addition, preliminary studies show that cells from osteoporotic bone have a severely reduced proliferative capacity. This model of bone cell aging facilitates study of the molecular mechanisms of osteoblast senescence as well as factors related to osteoblast dysfunction in patients with osteoporosis.
TL;DR: It seems that even daily chores, such as climbing stairs and walking, protect against hip fracture, and to be among the physically active seems to reduce the risk of later hip fracture by up to 50%.
Abstract: Studies on the association between physical activity and hip fractures are reviewed. All the studies, which comprise four follow-up studies, one nested case-control study and 17 case-control studies, suggest a protective effect of physical activity with regard to hip fractures. The association is strong and consistent with physical activity in leisure, weaker with respect to physical activity at work. The association is present for physical activity from childhood to adult age, and it is consistent in study populations from the USA, Australia, Asia and Northern and Southern Europe, in spite of very different hip fractures incidences in these populations. The magnitude of the association is difficult to assess because of varying criteria for exposure, but to be among the physically active seems to reduce the risk of later hip fracture by up to 50%. It seems that even daily chores, such as climbing stairs and walking, protect against hip fracture.
TL;DR: There are, however, few convincing data to suggest that peak bone mass can be influenced by therapeutic strategies, so that the determination of risk of individuals is more appropriately targeted in later life.
Abstract: The incidence of many types of fracture increases logarithmically with age in both sexes and a great deal of evidence indicates that this is causally related to the changes in the amount of bone tissue present at these sites. The factors involved in the amount of bone present and hence the risk of fractures in adult life are peak bone mass attained in early adulthood and the amount of bone lost, for example, during the course of disease or after the menopause. The determinants of the peak bone mass and bone loss differ and both may be affected by diseases, environmental factors and by treatment. There are, however, few convincing data to suggest that peak bone mass can be influenced by therapeutic strategies [1,2], so that the determination of risk of individuals is more appropriately targeted in later life. The loss of bone that occurs in osteoporosis is associated with several other structural and qualitative abnormalities that contribute to the loss of skeletal strength. These include changes in the tumover of bone and hence the rate of repair of fatigue damage, and the loss of connectivity of the trabecular elements which comprise cancellous bone. These and other abnormalities are collectively termed alterations in the quality of bone. Although these contribute to skeletal weakness, some of these changes in the quality of bone are the direct consequence of bone loss itself. Over and above this, bone mass is not the sole determinant of fracture risk. For any given bone mass, the risk of fracture is greater in the elderly, in part because of an increased tendency to fall and a decreased ability to react appropriately to diminish the force of impact. For these reasons the contribution of peak bone mass, skeletal and extraskeletal factors to hip fracture risk varies according to age [1,3]. Despite this multiplicity of factors, attention has focused on the measurement of bone mass rather than other determinants of fracture risk, largely because of the variety of non-invasive techniques that are now available for the measurement of bone mineral content or bone mineral density (BMD). Moreover, osteoporosis is
TL;DR: The study of age-dependent changes in mean BMD and standard deviation at the lumbar spine and femoral neck in a normal population extracted from 4280 women screened for osteopenia and compared with the manufacturer's normal range finds that manufacturer's reference ranges may not be appropriate for the local population and may lead to an erroneously high diagnosis.
Abstract: Osteoporosis is a common disease which causes significant morbidity and mortality and in many cases may be preventable. In the absence of fragility fractures the accepted method of identifying those at high risk is based upon bone mineral density (BMD) measurements with defined cut-off points. To correctly delineate normal from abnormal, reliable reference ranges appropriate to the observed population are required. We have studied the age-dependent changes in mean BMD and standard deviation at the lumbar spine and femoral neck in a normal population extracted from 4280 women screened for osteopenia and compared our findings with the manufacturer's normal range (MNR). The recent World Health Organization criteria for the diagnosis of osteopenia and osteoporosis using the 'manufacturer's young normal' (MYN) values and our 'study young normal' (SYN) values have been applied. The study normal population (SNP) included 2068 women (mixed social class; mean age 53 years, range 30-79 years). The distribution of mean lumbar spine BMD with age in SNP was generally similar to the MNR. In contrast mean femoral neck bone density from SNP was significantly different from the MNR, ranging from 3% to 12% lower in each 5-year group analysed (p < 0.05). Comparison of standard deviations in spine BMD in SNP against the fixed MNR standard deviation showed a statistically significant increase commencing at 45 years of age. The magnitude of this increase appeared to rise with age and remained significant in the 75- to 79-year age group (p < 0.05). In contrast, standard deviation in femoral neck BMD in SNP appeared relatively constant with age except in the group of women at and around the time of the menopause. The SYN value for mean lumbar spine BMD was 0.994 g/cm2 (cf. MYN value 1.047, p < 0.0001) with a standard deviation of 0.122 g/cm2 (cf. MYN 0.11, p = 0.0005). Similarly our SYN value for femoral neck BMD was 0.787 (cf. MYN value 0.895, p < 0.0001) with a standard deviation of 0.109 (cf. MYN value 0.10, p = 0.0027). Using SYN values 36% (748) for the spine and 33% (675) for the hip of our normal population are classified as osteopenic or osteoporotic. Using MYN values increases the proportion of women classified as osteopenic or osteoporotic to 52% (1078) for the spine and 68% (1409) for the femur. If both sites of measurement are considered simultaneously SYN classifies 46% (952) as either osteopenic or osteoporotic at one or other site, which is increased to 73% (1513) when the MYN values are used. We observe that manufacturer's reference ranges may not be appropriate for the local population and may lead to an erroneously high diagnosis of osteopenia and osteoporosis, which would lead to unnecessary patient anxiety and perhaps errors regarding treatment.
TL;DR: This study demonstrates that measurement of the AD-SoS at the phalanx is reproducible, can be employed to assess the risk of fracture, and is able to detect age-related alterations in bone tissue.
Abstract: A longitudinal study was conducted to assess the value of quantitative ultrasound (QUS) measurement in predicting the risk of fracture and to evaluate how QUS parameters change with ageing and the climacteric. A group of 211 female subjects underwent assessment by QUS at the distal metaphysis of the first phalanx of the last four fingers of the hand on two occasions 3 years apart. The subjects were selected from outpatients attending the orthopaedic clinic, provided they were not affected by metabolic disease or under treatment with drugs known to interfere with bone metabolism. In vivo the coefficient of variation and the standardized coefficient of variation of the QUS device were respectively 0.5% and 3.5%. The correlation between the values of the amplitude-dependent speed of sound (AD-SoS) in the two measurements was r = 0.92. In 77.3% of the subjects during the observation period we recorded a reduction in AD-SoS. During the study 22 fractures were observed in peripheral sites, 8 of which were associated with 'low-energy trauma'. By multiple logistic regression analysis we found that the relative risk of fracture for a 1 SD reduction in AD-SoS was 1.5 (95% CI 1.1-1.7) (p < 0.03). The percentage of low-energy fractures significantly increased among those subjects with an AD-SoS value lower than 1850 m/s (T-score < -3.5) at the first examination (p <0.0001). QUS investigation proved to be especially sensitive to hormonal changes associated with the climacteric: we observed a mean decrease of 56 m/s in the AD-SoS for women who entered the menopause between the first and the second QUS test (average time since menopause 2 years), as against 10 m/s in subjects remaining premenopausal. In a group of 146 subjects with 'normal' Ad-SoS at the first examination, we observed a significant reduction in AD-SoS only after 40 years of age. This study demonstrates that measurement of the AD-SoS at the phalanx is reproducible, can be employed to assess the risk of fracture, and is able to detect age-related alterations in bone tissue.
TL;DR: Increased apparent density of the OA trabecular bone resulted in a greater stiffness, yield strength and energy absorbed to yield, whereas the same properties of OP bone were not significantly lower than normal.
Abstract: Patients with osteoarthritis (OA) rarely fracture the neck of the femur whereas this is common in patients with osteoporosis (OP). The reasons for this are not clear. In this study, cores of trabecular bone and thin slices of bone from the calcar were obtained from the femoral neck of patients with OA or OP following hip arthroplasty and a normal group post mortem. The mechanical properties, densities and material composition were measured. The aim was to determine whether differences in these properties could explain why osteoarthritic patients did not suffer from fractured neck of femur. No difference was found in the density or stiffness of the calcar between the groups, though there appeared to be a small increase in mineralization in the OA bone compared with the OP. However, there was a 72% increase in the volume of trabecular bone in the OA group compared with a loss of about 20% in the OP group. This increased apparent density of the OA trabecular bone resulted in a greater stiffness, yield strength and energy absorbed to yield, whereas the same properties of OP bone were not significantly lower than normal. These marked changes in the OA bone could result in a redistribution of stresses due to loads caused by falling, thereby absorbing the energy of impact and preventing the formation of a fracture surface.
TL;DR: The potential benefit of thiazide diuretics for osteoporosis should be considered when prescribing antihypertensive treatment.
Abstract: Thiazide diuretics reduce urinary calcium and may inhibit bone resorption, and hence may help to attenuate age-related bone loss and to lower the risk of osteoporotic fracture. We followed 83 728 women, who were 36–61 years of age at baseline in 1982, for 10 years with biennial mailed questionnaires on which they reported incident fractures, use of thiazide diuretics, and other medical behavioral information. From descriptions of fracture sites and circumstances, 251 hip (proximal femur) and 1594 forearm (distal radius) fractures were identified as low or moderate trauma events. After controlling for age, body mass index, menopausal status, postmenopausal hormone use, cigarette smoking and dietary factors, we observed a statistically significant 22% reduction in the risk of forearm fractures among current thiazide users compared with women who reported no thiazide use. Risk appeared to decline with longer duration of use, reaching a 37% reduction in risk among women who had been using thiazides for 8 or more years. For hip fractures, thiazide use was protective among the postmenopausal women (relative risk = 0.69, 95% confidence interval 0.48–0.99). We conclude that the potential benefit of thiazide diuretics for osteoporosis should be considered when prescribing antihypertensive treatment.
TL;DR: The very high correlation between attenuation and frequency found in all ROIs suggests that measurement errors of propagation were probably not significant, and suggests the opportunity for studying the spatial acoustic properties in the calcaneus and their relation to bone mass or structural parameters provided by independent imaging techniques.
Abstract: The purposes of this study was to determine the relationship between broadband ultrasound attenuation (BUA) and bone mineral density (BMD) measured at different regions of the calcaneus with identical site-matched regions of interest (ROIs). Dual-energy X-ray absorptiometry (DXA) measurements of the calcaneus and BUA imaging were performed in 30 women (15 premenopausal and 15 postmenopausal). Four square ROIs were located in the great tuberosity and one square ROI in the foramen calcaneus. A ROI adapted to the shape and size of the whole calcaneus was also considered. All ROIs were analyzed three times with both techniques to minimize intra-observer variability. The correlation coefficient between attenuation and frequency was used as an index of BUA measurement error. Before accepting a measurement of BUA in inhomogeneous material, it could be useful to map the spatial variations of the measurement error. In all ROIs we found the BUA and BMD were strongly related (r=0.78−0.91,p<0.001). The correlation between BUA and BMD was slightly higher in the inferior part of the posterior tuberosity than in the superior part and in the foramen calcaneus. The very high correlation between attenuation and frequency found in all ROIs (r=0.99) suggests that measurement errors of propagation were probably not significant. Ultrasound imaging yields the opportunity for studying the spatial acoustic properties in the calcaneus and their relation to bone mass or structural parameters provided by independent imaging techniques. BUA measured with current transmission techniques reflects mainly bone mass, and microarchitecture to a smaller extent.
TL;DR: Protein intake below the RDA could be particularly detrimental for both the acquisition of bone mass and the conservation of bone integrity with aging and, therefore, can be expected to affect peak bone mass.
Abstract: Deficiency in nutritional elements could play an important role in the pathogenesis of osteoporotic fracture in the elderly. Results of several studies indicate that calcium supplementation reduces bone loss and fracture incidence in vitamin D replete elderly subjects [1]. Other investigations have suggested that the level of protein intake could influence either calcium phosphate metabolism, bone mass or the risk of osteoporotic fracture [2]. Apparently contradictory information suggests that either a deficient or an excessive protein supplement could negatively affect the balance of calcium and the arnount of bony tissue contained in the skeleton [2,3]. Several reasons can be evoked with respect to the present uncertainty regarding the effect of protein supplementation on calcium balance and bone mass. The outcomes may differ because the protein supplementation was: (a) prescribed either to wellnourished people or to subjects exhibiting signs of malnutrition; (b) given in various forms: natural food products (i.e. ingested in complex forms), purified extracts or mixtures of amino acids; (c) of either animal (e.g. casein) or vegetable (e.g. soya) origin; (d) evaluated over either the short term or the long term; (e) assessed in the presence or absence of modifications in other nutritional factors such as energy and/or calcium. The recommended daily allowance (RDA) for protein varies from 2.0 g/kg body weight in children to 1.0 g/kg in adolescents, and 0.75 g/kg in adults [4]. Protein intake below the RDA could be particularly detrimental for both the acquisition of bone mass and the conservation of bone integrity with aging. Protein undemutrition during childhood and adolescence results in a reduction of height, weight and overall body protein [5] and, therefore, can be expected to affect peak bone mass. A sufficient protein intake is also mandatory for the maintenance of bone homeostasis during adulthood. In the elderly, malnutrition can be considered as a risk factor for hip fracture because it can accelerate age-
TL;DR: The aims of this study were to quantify the hospital burden of vertebral fracture in Europe and to compare this with that of hip fracture, and to suggest a relationship between hip and vertebra fracture risk that is not explained by different admission policies for vertebral fractures in different European countries.
Abstract: The aims of this study were to quantify the hospital burden of vertebral fracture in Europe and to compare this with that of hip fracture. Information on hospital discharges was sought by age and sex from Ministries of Health in Europe. Discharge rates for vertebral fracture, available from 12 countries, varied by more than 4-fold between countries, which was greater than the differences between sexes. Where the discharge rate was high for vertebral fracture the incidence of hip fracture was also high. Since nearly all cases of hip fracture are hospitalized, this suggests a relationship between hip and vertebral fracture risk that is not explained by different admission policies for vertebral fracture in different European countries.
TL;DR: The lack of effect shown in the present study may be explained by insufficient dose regimen and/or impaired absorption from the intestinal tract and further investigations are needed to define future dose regimens in order to validate the effect on bone mass, fracture rate and biochemical markers.
Abstract: This paper presents the results of a two-center, double-masked, placebo-controlled, randomized, oral-dose study of risedronate treatment in postmenopausal osteoporosis. Patients had at least one, but no more than four prevalent vertebral fractures at baseline. They received either 2.5 mg continuous risedronate, 2.5 mg cyclic risedronate, or placebo for 2 years. Both risedronate and placebo were formulated as hard gelatin capsules. All women furthermore received a daily calcium supplement of 1 g which was taken separately from the study drug. During the 1-year of follow-up, all women received only a daily calcium supplement of 1 g. A total of 132 patients were enrolled (44 in each treatment group), of which 73% completed the 2-year treatment period and 70% all 3 years. Generally the outcome of the study was negative. Lumbar spine bone mineral density (BMD) increased 1.2% (NS) and 0.8% (NS) and after 2 and 3 years in the group treated with continuous risedronate, 1.7% (NS) and 2.3% (p < 0.05) in the group treated with cyclic risedronate, and 0.6% (NS) and 1.7% (NS) in the placebo group. BMD in the femoral neck increased 2.9% (p < 0.05) and 0.9% (NS) after 2 and 3 years in the group treated with continuous risedronate, 1.3% (NS) and 2.4% (p < 0.01) in the group treated with cyclic risedronate, and 1.3% (NS) and 2.6% (p < 0.01) in the placebo group. The differences between all three groups in spinal and femoral BMD after 2 years were not statistically significant, bur reached statistical significance after 3 years (p < 0.01) in the femoral neck. Only minor changes were observed in the measured markers of bone turnover. Both the incidence and rate of new vertebral fractures showed no overall differences between the groups. The distribution of adverse events was similar across treatment groups. None of the serious adverse events were considered causally related to risedronate. The lack of effect shown in the present study may be explained by insufficient dose regimen and/or impaired absorption from the intestinal tract. Further investigations (ongoing phase III trials) are needed to define future dose regimens in order to validate the effect on bone mass, fracture rate and biochemical markers. In these studies another formulation of the drug and other dosing instructions are used.
TL;DR: The results suggest that vertebral deformity and size make only a minor contribution to the prediction of vertebral strength additional to that provided by bone densitometry alone.
Abstract: The estimation of vertebral fracture risk in individuals with suspected osteopenia is commonly based on measurements of lumbar spine bone density. The efficacy of vertebral size and deformity, as assessed by vertebral morphometry, in the prediction of fractures has been less studied. In an ex vivo investigation the regional relationships between vertebral size, vertebral deformity, bone density and compressive strength throughout the thoracolumbar spine were examined. In 16 vertebral columns (T1–L5) the bone mineral content (BMC) and bone mineral density (BMD) of each segment were measured using lateral projection dual-energy X-ray absorptiometry, and the vertebral cancellous density (VCD) and mid-vertebral cross-sectional area (CSA) measured using quantitative computed tomography. Vertebral body heights were determined from mid-sagittal CT scans, and vertical height ratios calculated for each segment. The failure load and failure stress of the isolated vertebral bodies were determined using a material testing device. Separate analyses were performed for the upper (T1–4), middle (T5–8) and lower (T9–12) thoracic, and lumbar (L1–5) segments. In all regions, failure load was strongly correlated with BMD (r=0.82–0.86), moderately correlated with VCD (r=0.60–0.71) and vertebral height (r=0.22–0.49), and poorly correlated with the height ratios (r=0.04–0.33). Failure stress was best predicted by BMD (r=0.73–0.78) and VCD (r=0.70–0.78) but was poorly correlated with all morphometric variables (r=0.01–0.33). The segmental correlations between BMD and VCD ranged fromr=0.49 tor=0.79. For all regions, BMD and VCD were included in the stepwise regression models for predicting failure load and failure stress. Either the mid-vertebral height or CSA were included in all the failure load models, while mid-vertebral height was included in only one of the failure stress models. The results suggest that vertebral deformity and size (as assessed by vertebral morphometry) make only a minor contribution to the prediction of vertebral strength additional to that provided by bone densitometry alone. The consistent regional relationships between variables appear to support the practice of global fracture risk assessment based on lumbar spine densitometry.
TL;DR: The results suggest that the higher peak femoral neck BMD in South African blacks than in whites might be determined by greater weight-bearing in blacks and that the significantly lower femoral necks BMD on average in postmenopausal whites than in blacks is determined by lower peak Femoral Neck BMD and a faster post menopausal decline in B MD in whites.
Abstract: In South Africa, appendicular and lumbar spine bone mineral density (BMD) have been found to be similar in black and white women. However, femoral BMD has been found to be higher in black than in white women. Two different techniques were used to recalculate BMD to eliminate the possible confounding influence of ethnic differences in height on areal BMD measurements. Volumetric bone mineral apparent density (BMAD) values were calculated and bone mineral content (BMC) was corrected for body and bone size. This report analyses differences in BMD (corrected for height and weight), BMAD, BMC (corrected for body and bone size), femoral neck axis length (FNAL), mineral homeostasis and bone turnover (BT) in a group of 20 to 49-year-old premenopausal (105 whites and 74 blacks) and 45 to 64-year-old postmenopausal (50 whites and 65 blacks) female South African nurses. The corrected BMD and BMC findings were congruous, showing that both pre- and postmenopausal blacks and whites have similar distal radius and lumbar spine bone mass but that whites have lower femoral neck bone mass than blacks. In contrast, BMAD findings suggest that pre- and postmenopausal whites have lower bone mass at the lumbar spine and femoral neck than blacks but similar bone mass at the distal radius to blacks. There is a greater rate of decline in BMD in postmenopausal whites than in blacks. BMD at the femoral neck was 12.1% lower in premenopausal whites and 16.5% lower in postmenopausal whites than in blacks. There was a positive association between femoral neck BMD and weight in premenopausal blacks (R2=0.5,p=0.0001) but not in whites. Blacks had shorter FNAL than whites in both the pre- and postmenopausal groups. Blacks had lower serum 25-hydroxyvitamin D (25-(OH)D) and higher 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels than whites. There were no ethnic differences in biochemical markers of bone formation (serum alkaline phosphatase and osteocalcin) or bone resorption (urine hydroxyproline and pyridinoline), or in dietary calcium intake in either the pre- or postmenopausal groups. In the postmenopausal group, whites had higher ionized serum calcium (p=0.003), similar serum albumin, lower serum parathyroid hormone (p=0.003) and higher urinary calcium excretion (p=0.0001) than blacks. These results suggest that the higher peak femoral neck BMD in South African blacks than in whites might be determined by greater weight-bearing in blacks and that the significantly lower femoral neck BMD in postmenopausal whites than in blacks is determined by lower peak femoral neck BMD and a faster postmenopausal decline in BMD in whites. The higher incidence of femoral neck fractures in South African whites than in blacks is probably determined by the lower femoral neck BMD and longer FNAL in whites. The greater rate of decline in BMD in postmenopausal whites than in blacks is associated with an increase in urinary calcium excretion in whites. Measurement of biochemical markers of BT has not contributed to the understanding of ethnic differences in BMD and skeletal metabolism in our subjects.