Associations of vertebral deformities and osteoarthritis with back pain among Japanese women: the Hizen-Oshima study.

UNLABELLED: We examined the spinal distribution of the types of vertebral deformities and the associations of vertebral deformities and osteoarthritis with back pain in Japanese women. Midthoracic and upper lumbar vertebrae were more susceptible to deformity. Vertebral deformity and osteoarthritis were frequent and were associated with back pain. INTRODUCTION: Vertebral fractures due to osteoporosis and osteoarthritis are both common and significant health problems in aged people. However, little is known about the descriptive epidemiology of the individual deformity types and the relative clinical impact in women in Japan. METHODS: Lateral radiographs were obtained from 584 Japanese women ages 40 to 89 years old. Deformities were defined as vertebral heights of more than 3 standard deviations (SDs) below the normal mean. Osteoarthritis was defined as Kellgren-Lawrence (KL) grade 2 or higher. Information on upper or low back pain during the previous month was collected by questionnaire. We compared the spinal distribution of the three types of vertebral deformities (wedge, endplate, and crush) typical of fractures and examined the associations of number and type of vertebral deformities and osteoarthritis with back pain. RESULTS: Fifteen percent of women had at least one vertebral deformity and 74% had vertebral osteoarthritis. The prevalence of upper or low back pain was 30.1%. Deformities were most common in the midthoracic and upper lumbar regions and wedge was the frequent type, followed by endplate and crush. Multiple logistic regression analysis showed that the odds of back pain was 3.0 (95% CI 1.5-6.3) times higher for women with a single wedge deformity and 3.2 (95% CI 1.0--0.6) times higher for women with two or more wedge deformities, compared to women with no wedge deformity. Vertebral osteoarthritis was associated with back pain (OR 1.8, 95% CI 1.1-2.9), independent of other covariates including age and deformities. CONCLUSION: Our results in this group of Japanese women are similar to and consistent with results reported previously in other populations of Japanese and Caucasians.

A case series and literature review on patients with rhinological complications secondary to the use of cocaine and levamisole.

BACKGROUND: Levamisole is an increasingly common cutting agent used with cocaine. Both cocaine and levamisole can have local and systemic effects on patients. METHODS: A retrospective case series was conducted of patients with a cocaine-induced midline destructive lesion or levamisole-induced vasculitis, who presented to a Dundee hospital or the practice of a single surgeon in Paisley, from April 2016 to April 2019. A literature review on the topic was also carried out. RESULTS: Nine patients from the two centres were identified. One patient appeared to have levamisole-induced vasculitis, with raised proteinase 3, perinuclear antineutrophil cytoplasmic antibodies positivity and arthralgia which improved on systemic steroids. The other eight patients had features of a cocaine-induced midline destructive lesion. CONCLUSION: As the use of cocaine increases, ENT surgeons will see more of the complications associated with it. This paper highlights some of the diagnostic issues and proposes a management strategy as a guide to this complex patient group. Often, multidisciplinary management is needed.

Vitamin D status and falls, frailty, and fractures among postmenopausal Japanese women living in Hawaii.

UNLABELLED: Vitamin D status and its relationship to physical performance, falls, and fractures in 495 postmenopausal women of Japanese ancestry in Hawaii were investigated. The mean 25-hydroxyvitamin D (25-OHD) was 31.94 ng/mL. No significant association of 25-OHD was demonstrated with most outcomes, possibly due to higher 25-OHD levels in this population. INTRODUCTION: In this study, we investigated vitamin D status and its relationship to physical performance, muscle strength, falls, and fractures in postmenopausal Japanese females living in Hawaii. METHODS: Of 510 community-dwelling women who participated in the eighth examination of the Hawaii Osteoporosis Study, 495 were included in these analyses. Multivariate regression models were used to evaluate the relationship of 25-OHD (D(3) and total) to eight performance-based measurements, 12 activities of daily living (ADLs), and muscle strength (grip, triceps, and quadriceps). Logistic regression analyses were performed to evaluate the relationship of 25-OHD to falls, vertebral fractures, and non-vertebral fractures. RESULTS: The mean total 25-OHD was 31.94 +/- 9.46 ng/mL; 44% of subjects had values <30 ng/mL, while none had values <10-12 ng/mL. There was little evidence of seasonal variation. Among performance-based measures, ADLs, and strength tests, only quadriceps strength was significantly associated with total 25-OHD (p = 0.0063) and 25-OHD(3) (p = 0.0001). No significant association of 25-OHD was found with vertebral or non-vertebral fractures, or incidence of one or more falls. CONCLUSIONS: Lack of serum 25-OHD relationship with falls and fractures or most physical performance measures in this study may be related to the low prevalence of very low 25-OHD levels in this population.

Conformational changes of a viral capsid protein. Thermodynamic rationale for proteolytic regulation of bacteriophage T4 capsid expansion, co-operativity, and super-stabilization by soc binding.

We have used differential scanning calorimetry in conjunction with cryo-electron microscopy to investigate the conformational transitions undergone by the maturing capsid of phage T4. Its precursor shell is composed primarily of gp23 (521 residues): cleavage of gp23 to gp23* (residues 66 to 521) facilitates a concerted conformational change in which the particle expands substantially, and is greatly stabilized. We have now characterized the intermediate states of capsid maturation; namely, the cleaved/unexpanded, state, which denatures at tm = 60 degrees C, and the uncleaved/expanded state, for which tm = 70 degrees C. When compared with the precursor uncleaved/unexpanded state (tm = 65 degrees C), and the mature cleaved/expanded state (tm = 83 degrees C, if complete cleavage precedes expansion), it follows that expansion of the cleaved precursor (delta tm approximately +23 degrees C) is the major stabilizing event in capsid maturation. These observations also suggest an advantage conferred by capsid protein cleavage (some other phage capsids expand without cleavage): if the gp23-delta domains (residues 1 to 65) are not removed by proteolysis, they impede formation of the stablest possible bonding arrangement when expansion occurs, most likely by becoming trapped at the interface between neighboring subunits or capsomers. Icosahedral capsids denature at essentially the same temperatures as tubular polymorphic variants (polyheads) for the same state of the surface lattice. However, the thermal transitions of capsids are considerably sharper, i.e. more co-operative, than those of polyheads, which we attribute to capsids being closed, not open-ended. In both cases, binding of the accessory protein soc around the threefold sites on the outer surface of the expanded surface lattice results in a substantial further stabilization (delta tm = +5 degrees C). The interfaces between capsomers appear to be relatively weak points that are reinforced by clamp-like binding of soc. These results imply that the "triplex" proteins of other viruses (their structural counterparts of soc) are likely also to be involved in capsid stabilization. Cryo-electron microscopy was used to make conclusive interpretations of endotherms in terms of denaturation events. These data also revealed that the cleaved/unexpanded capsid has an angular polyhedral morphology and has a pronounced relief on its outer surface. Moreover, it is 14% smaller in linear dimensions than the cleaved/expanded capsid, and its shell is commensurately thicker.

Assembly-dependent conformational changes in a viral capsid protein. Calorimetric comparison of successive conformational states of the gp23 surface lattice of bacteriophage T4.

Inter- and intra-subunit bonding within the surface lattice of the capsid of bacteriophage T4 has been investigated by differential scanning calorimetry of polyheads, in conjunction with electron microscopy, limited proteolysis and sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The bonding changes corresponding to successive stages of assembly of the major capsid protein gp23, including its maturation cleavage, were similarly characterized. The uncleaved/unexpanded surface lattice exhibits two endothermic transitions. The minor event, at 46 degrees C, does not visibly affect the surface lattice morphology and probably represents denaturation of the N-terminal domain of gp23. The major endotherm, at 65 degrees C, represents denaturation of the gp23 polymers. Soluble gp23 from dissociated polyheads is extremely unstable and exhibits no endotherm. Cleavage of gp23 to gp23* and the ensuing expansion transformation effects a major stabilization of the surface lattice of polyheads, with single endotherms whose melting temperatures (t*m) range from 73 to 81 degrees C, depending upon the mutant used and the fraction of gp23 that is cleaved to gp23* prior to expansion. Binding of the accessory proteins soc and hoc further modulates the thermograms of cleaved/expanded polyheads, and their effects are additive. hoc binding confers a new minor endotherm at 68 degrees C corresponding to at least partial denaturation of hoc. Denatured hoc nevertheless remains associated with the surface lattice, although in an altered, protease-sensitive state which correlates with delocalization of hoc subunits visualized in filtered images. While hoc binding has little effect on the thermal stability of the gp23* matrix, soc binding further stabilizes the surface lattice (delta Hd approximately +50%; delta t*m = +5.5 degrees C). It is remarkable that in all states of the surface lattice, the inter- and intra-subunit bonding configurations of gp23 appear to be co-ordinated to be of similar thermal stability. Thermodynamically, the expansion transformation is characterized by delta H much less than 0; delta Cp approximately 0, suggesting enhancement of van der Waals' and/or H-bonding interactions, together with an increased exposure to solvent of hydrophobic residues of gp23* in the expanded state. These findings illuminate hypotheses of capsid assembly based on conformational properties of gp23: inter alia, they indicate a role for the N-terminal portion of gp23 in regulating polymerization, and force a reappraisal of models of capsid swelling based on the swivelling of conserved domains.

Osteoporosis Current practice and future perspectives.

Initiation of estrogens or other drugs as preventive measures for osteoporosis should be based upon objective estimates of actual, future fracture risk. Bone mass measurements, when considered in the context of age, life expectancy, expected bone loss, and other risk factors, enable improved patient risk stratification, and more rational treatment choices.

Osteoporosis. Frequency, consequences, and risk factors.

More than half of all women and about one third of men will experience osteoporotic fractures during their lives. Although no symptoms occur prior to fracture, bone mineral density and other risk factors can be used to identify high-risk patients, and because effective interventions exist, many of these fractures are now preventable. The proportion of people who are affected, the mortality and morbidity resulting from osteoporotic fractures, and the major known risk factors are discussed. Greater attention should be given to measuring bone mineral density and identifying other risk factors to quantitate the degree of fracture risk among patients (with or without a history of previous fractures), because the consequences of fractures often are severe, and no symptoms other than fractures are associated with disease progression.

Vertebral fracture and other predictors of physical impairment and health care utilization.

BACKGROUND: A better understanding of the impact of vertebral fractures on physical functioning would help clinicians gauge the potential benefits of identifying patients at high risk and prevent vertebral fractures due to osteoporosis. METHODS: We explored the associations of vertebral fractures and other potential predictors with physical impairment and health care utilization based on the data collected from 569 postmenopausal Japanese American participants of the Hawaii Osteoporosis Study, aged from 55 to 93 years. A major advantage of this study is the availability of serial spine radiographs for all participants. All vertebral fractures could be identified and the fracture dates estimated. RESULTS: Poor physical functioning was related to increases in number of recent vertebral fractures, age, body mass index, and number of other painful joints. Recent vertebral fractures had a strong impact on bending- and walking-related activities. For each recent vertebral fracture, the odds of impairment increased about 2 times and the odds of a physician visit for back pain increased 3.6 times. The number of recent vertebral fractures was also a significant predictor of poor performance in functional reach and walking speed tests. The effects of vertebral fractures on physical functioning may persist for several years. CONCLUSIONS: Recent vertebral fractures may lead to long-term poor physical functioning. Clinicians should take appropriate measures to identify those at risk, to prevent progression of osteoporosis, and to limit associated disability.

Rapid bone loss is associated with increased levels of biochemical markers.

We examined associations of biochemical markers of bone turnover with rapid bone loss, as measured by changes in bone mineral density (BMD). To improve the precision of bone loss estimates, calcaneal BMD was measured up to eight times over a long interval (13 years) among postmenopausal women (mean age = 62 years at baseline). Women with fractures during the previous year, and users of corticosteroids, active vitamin D, bisphosphonates or calcitonin were excluded to avoid potential transient effects on marker levels. Among the remaining 354 women, markers were measured for 100 women with the fastest BMD loss (rapid loss group; mean = 2.2%/year) and 100 with the slowest loss (mean = 0.4%/year). Two markers of bone formation, serum bone alkaline phosphatase (Alkphase-B; BAP) and osteocalcin (NovoCalcin; OC), and two markers of bone resorption, urinary creatinine-corrected free deoxypyridinoline (Pyrilinks-D; DPD) and free pyridinolines (Pyrilinks; PYD), were measured. In separate logistic regression models, each of the markers was strongly associated with rapid loss: the odds of rapid loss increased by 1.8 to 2.0 times for each 1.0 standard deviation (SD) increase of the marker. For BAP levels 2 SD above the mean, the probability of rapid bone loss was 80%; in contrast, the probability was only 20% at 2 SD below the mean. The other markers yielded similar results. We conclude that these markers are associated with rapid bone loss; this relationship appears to be continuous, with progressively greater risk of rapid bone loss with increasing levels of biomarkers. Prospective studies that include the entire distribution of bone loss rates are warranted to confirm these findings.

Vertebral fractures and other predictors of back pain among older women.

We examined the prevalence and predictors of back pain (BKP) among 645 postmenopausal Japanese-American women in Hawaii with a mean age of 73.9 years (ranging from 55 to 93 years) and serial spine radiographs during the preceding 12 years. The overall prevalence of BKP was 32.9% and appeared to be constant up to age 80, with an increase thereafter. At most ages, pain in the lower back was the most common, upper BKP was less so, and mid-BKP was the least common. The overall prevalence of BKP among Japanese-American women in Hawaii was about half of that reported for U.S. Caucasians. Vertebral fractures were divided into three categories based on the length of time since the fracture was identified on radiographs. BKP was only associated with recent vertebral fractures (during the previous 4 years, on average) and increased progressively with the number and severity of fractured vertebrae. A history of a single recent fracture was associated with a 2.8-fold increase in the odds of BKP; two recent fractures with a 7.8-fold increase and three recent fractures with a 21.7-fold increase in the odds of BKP. In addition, self-reported disk problems, body mass index, and the number of other painful joints also showed independent associations with BKP. Height, spine bone mineral density (BMD), calcaneus BMD, smoking, and number of live births were not significantly associated with BKP.

Short-term and long-term fracture prediction by bone mass measurements: a prospective study.

Prospective and cross-sectional studies have demonstrated that bone mass predicts fracture risk. However, most prospective studies have been limited to a few years of follow-up. We investigated the long-term associations of bone mass with vertebral fractures using longitudinal data collected from more than 500 postmenopausal Japanese-American women in the Hawaii Osteoporosis Study. New vertebral fractures were identified during an average of 2.7 years between 1992 and 1995. Short-term fracture prediction was evaluated using bone mass (spine, calcaneus, distal radius, and proximal radius) measured at the beginning of follow-up. Long-term prediction was evaluated using bone mass measured before the follow-up period (11 years earlier for nonspine bone mass and 8 years earlier for spine). All four bone mass measurements were significant predictors of vertebral fractures identified during the subsequent 2.7 years (short-term prediction), with odds ratios (ORs) ranging from 1.5 to 1.9. The ORs for long-term prediction were slightly lower in magnitude, but the confidence intervals overlapped the short-term ORs considerably, suggesting that both long-term and short-term associations are similar in magnitude. Furthermore, cross-sectional analyses based on bone mass measurements performed at the end of follow-up (after fractures had occurred) yielded results similar to those based on prospective data (bone mass measured prior to fractures), suggesting that the relatively quick and inexpensive cross-sectional studies are useful for preliminary evaluations of new bone mass measurement techniques. The results suggest that bone mass measurements made up to 11 years earlier can predict vertebral fractures almost as well as measurements made more recently.

Detection of prefracture spinal osteoporosis using bone mineral absorptiometry.

Bone mineral measurements have been criticized for their inability to clearly distinguish fracture and "nonfracture" populations. However, this failure is not unexpected, since some individuals in the "nonfracture" group have low bone mass and are at increased risk but have not yet experienced fractures. Although standard radiographs are not sensitive indicators of vertebral demineralization, they do identify some of the "prefracture" osteoporotic subpopulation within the nonfracture group. Prospective follow-up of 536 Japanese-American women demonstrated that 14 new spine fractures occurred in the prefracture osteoporosis group, whereas none occurred in the nonosteoporotic group (p less than or equal to 0.03). However, bone mineral content (BMC) measurements using photon absorptiometry were much more accurate than radiographs as indicators of spine fracture risk. BMC values were somewhat higher in the prefracture group than in those with existing fractures, but values for both groups were significantly lower than in nonosteoporotic patients even after adjusting for age, height, and weight (p less than 0.0001). The magnitude of the difference was proportional to the trabecular bone content of the measurement site; the differences were greatest for the os calcis and lumbar spine, smaller for the distal radius, and least for the proximal radius. The prevalence of spinal osteoporosis (including both fracture and prefracture cases) was inversely proportional to BMC (p less than 0.0001). Again, the relations were strongest for the os calcis and lumbar spine. These results indicate that BMC measurements are valid indicators of osteoporosis status, particularly when osteoporosis is defined to include both patients with existing fractures and those at increased risk for fractures. However, dual-photon spine BMC was adversely influenced by the presence of aortic calcification, arthritis, and other disease processes (p less than or equal to 0.0001).

Evidence for both generalized and regional low bone mass among elderly women.

The consistency of bone mass measurements across bone sites was examined in a cohort of elderly Japanese-American women. The study included 744 women of mean age 66.6 years (age range 47-82 years) who had bone densitometry measurements at the spine, calcaneus, and distal and proximal radius. The women were classified at the four bone sites as in the lower, middle, or upper bone mass tertile for their age. Slightly more than half (56%) of the women were in the lower tertile at one or more of the bone sites, and such women were usually in the lower category at more than one site. Of the women, 24% were classified in the lower tertile at all four sites. Furthermore, as a group, women classified as in the low bone mass category at any one site had a low average bone mass at all four sites. Prospectively, the number of low bone mass sites predicted the risk of new spine fractures after adjusting for age and the number of spine and nonspine prevalent fractures. The risk increased approximately 1.3-fold for each additional low bone mass site. A subgroup (15%) of the population had marked heterogeneity in bone mass between sites. These women had one or more lower tertile bone mass site(s) and one or more upper tertile bone mass site(s). The results suggest that osteoporosis may occur as either a generalized or as a regional disorder.

Comparison of cross-sectional and longitudinal measurements of age-related changes in bone mineral content.

Age-related, postmenopausal bone loss was examined among a cohort of Japanese-American women living in Hawaii. None of the women were using estrogens or thiazides. Cross-sectional and longitudinal measurements of bone mineral content were compared at the calcaneus, the proximal radius, and the distal radius. Cross-sectional measurements were also available for the lumbar spine. The longitudinal data showed a slowing rate of bone loss with increasing age at the radius sites. By contrast, the cross-sectional data suggested constant rates of bone loss for all ages at both radius sites and the spine. The calcaneus demonstrated a complex pattern of bone loss in both cross-sectional and longitudinal analyses. The loss rates among women in their fifties were greater than for those in their sixties. From the middle sixties onward calcaneal bone loss remained essentially constant. Because of the sustained bone loss, however, women in their seventies were actually losing greater percentages of their calcaneal bone mineral than they had in their sixties.

Relationship between bone mass and rates of bone change at appendicular measurement sites.

The rate of bone change among postmenopausal women may vary depending upon the initial bone mass. Examining this possibility is difficult, however, because of a negative statistical bias that occurs when change is regressed against the initial value of the same variable. In this article, four statistical methods were applied to measure the association between bone mass and the rate of bone change. The study population was Japanese-American women, who were monitored for approximately 5 years. Bone changes were determined for the calcaneus and the distal and proximal radius. The results were consistent across the bone sites but differed between statistical methods. Three of the four methods indicated that the women with the greater bone mass had the greater loss rates. The fourth method did not support this association. Possible reasons for the discordant results are discussed. Using the "best" estimate of the relationship, a gradual convergence of bone mass was projected over time toward the population mean. The convergence occurred because women with higher bone mass had a somewhat faster loss rate than women with lower bone mass. Overall, however, the variation in bone mass between individuals was large compared to the rate of convergence.

Blinded reading of radiographs increases the frequency of errors in vertebral fracture detection.

We examined the effect of blinding X-rays to film sequence and patient identity on vertebral fracture detection. A sample of 50 postmenopausal women with low bone density and two sets of spine X-rays 3.6 years apart was selected; based on prior morphometric studies, about half of the women had experienced new fractures after the initial film. New morphometric and semiquantitative radiologist readings were each performed twice: blinded and unblinded. For morphometry, incident fractures were defined as vertebral height decreases of more than 15% compared with the initial film. The incidence was slightly higher when blinded versus unblinded (5.6 vs. 5.3% of all vertebrae for morphometry, and 9.7 vs. 8.7% for the radiologist), but these differences were not significant. The error rate was investigated by examining the frequency of "fracture reversals"-vertebrae identified as fractured on the initial film but not on the later film. Agreement between blinded and unblinded readings was generally greater than 80% for fractures but less than 10% for "fracture reversals," suggesting that reversals are not true events but random errors. The number of reversals was higher when the radiologist was blinded (2.1% of all vertebrae vs. 0.8% when unblinded; p = 0.07). The number of vertebrae with increases greater than 15% in size over time was also greater when morphometry readings were blinded versus unblinded: 0.8 versus 0% (p < 0.05). Although these errors are small, they are similar in magnitude to the annual fracture incidence in many populations. These data show that blinding X-rays to sequence offers no advantages, increases the frequency of errors, and may inflate incidence rates. We conclude that the assessment of X-rays for vertebral fractures in clinical trials should not be performed with the evaluator blinded to the sequence of the X-rays.

The effects of smoking on bone mass and the rates of bone loss among elderly Japanese-American men.

Bone density and bone loss rates were examined among Japanese-American men categorized as current cigarette smokers, past smokers, and nonsmokers. The design included a retrospective study of smoking and bone density and a prospective study of current smoking and bone loss rates. The mean length of follow-up was 5 years; the setting was the island of Oahu. The subjects included 1303 men in the Hawaii Osteoporosis Study, 51-82 years old at their initial examination. Twenty percent were current smokers, 45% past smokers, and 35% had never smoked. Their bone density was measured at the distal and proximal radius and calcaneus using single photon absorptiometry. Compared with never smokers, current and past smokers had significantly lower bone density, especially in the predominantly cancellous calcaneus (4.8 and 4.3% lower, respectively) and partially trabecular distal radius (1.8 and 3.3% lower, respectively). The magnitude of the smoking effect was linked strongly to the duration of smoking and also to the number of cigarettes smoked. Bone loss rates subsequent to the initial measurement were greater in the current smokers than the never smokers (20.5, 27.2, and 9.7% greater at the calcaneus, distal, and proximal radius, respectively) but the differences did not achieve significance. Smokers of more than one pack per day had 32.0, 77.6, and 30.7% greater loss rates than never smokers in these same sites; the difference achieved significance at the distal radius. The results from the distal radius suggest that these smokers may increase their fracture risk 10-30% per decade of smoking. The adverse effects of smoking appeared to be greater in cancellous than cortical bone.

Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis.

Numerous studies have reported increased risks of hip, spine, and other fractures among people who had previous clinically diagnosed fractures, or who have radiographic evidence of vertebral fractures. However, there is some variability in the magnitudes of associations among studies. We summarized the literature and performed a statistical synthesis of the risk of future fracture, given a history of prior fracture. The strongest associations were observed between prior and subsequent vertebral fractures; women with preexisting vertebral fractures (identified at baseline by vertebral morphometry) had approximately 4 times greater risk of subsequent vertebral fractures than those without prior fractures. This risk increases with the number of prior vertebral fractures. Most studies reported relative risks of approximately 2 for other combinations of prior and future fracture sites (hip, spine, wrist, or any site). The confidence profile method was used to derive a single pooled estimate from the studies that provided sufficient data for other combinations of prior and subsequent fracture sites. Studies of peri- and postmenopausal women with prior fractures had 2.0 (95 % CI = 1.8, 2.1) times the risk of subsequent fracture compared with women without prior fractures. For other studies (including men and women of all ages), the risk was increased by 2.2 (1.9, 2.6) times. We conclude that history of prior fracture at any site is an important risk factor for future fractures. Patients with a history of prior fracture, therefore, should receive further evaluation for osteoporosis and fracture risk.

Perspectives: methodologic issues in evaluating risk factors for osteoporotic fractures.

Techniques for measuring bone mineral content (BMC) were developed for the purpose of providing an objective and noninvasive indication of bone strength (or lack thereof) and fracture risk, to the extent that strength relates to bone mass. As such, BMC measurements could help to (1) identify those who are most likely to experience nonviolent fractures in the future and who would therefore benefit most from preventive measures, (2) improve their treatment compliance, and (3) monitor the efficacy of treatments intended to reduce bone loss. All these potential uses require that the measurement provide an indication of fracture risk (probability of fractures). During the past 10-15 years there have been conflicting reports regarding the association of reduced BMC with nonviolent fractures. Some authors have criticized the usefulness of BMC measurements, whereas others have questioned the value of one or more techniques. However, the epidemiology of osteoporosis has only recently been subjected to rigorous study. The use of appropriate statistical methods for relating fracture risk to bone mass may be no more widely practiced in osteoporosis epidemiology today than it was for studying risk factors (e.g., blood pressure) in cardiovascular epidemiology during the 1960s. The intent of this article is to explore three areas that may have contributed to controversy in the study of bone mass and fracture occurrence: (1) perspective of the investigators, (2) study design, and (3) analytic methodology. Although the focus of this paper is on bone mass, these considerations are equally applicable to some investigations of other risk factors for osteoporotic fractures (e.g., bone architecture, bone turnover and loss rate, or biochemical markers of bone loss).

Falls among community-dwelling elderly in Japan.

Japanese have a lower incidence of hip fracture than Caucasians despite having lower bone mass. Hip fractures usually occur after a fall, and differing incidence rates of falls might explain the observed differences in hip fracture rates. To explore this hypothesis, we studied falls and related conditions among 1534 (624 men, 910 women) community-dwelling people aged 65 years and over in Japan and compared the prevalence of falls to Japanese-Americans living in Hawaii and to published studies of Caucasians. In Japan, 9% of the men and 19% of the women reported one or more falls during the past year. The prevalence of falls increased with age in both genders and was greater among women compared with men. In logistic regression models, having musculoskeletal disease, physical disability or limited activity increased the risk of falls by two to four times in both genders. Most fallers (92%) reported fear of future falls, and about one third of fallers reported that they went out less often as a result of their falls. Compared with native Japanese, the age-standardized prevalence of falls among Japanese-Americans was similar but about twice as high for Caucasians, which may explain the lower hip fracture risk of Japanese.