Worldwide prevalence and incidence of osteoporotic vertebral fractures.

We investigated the prevalence and incidence of vertebral fractures worldwide. We used a systematic Medline search current to 2015 and updated as per authors' libraries. A total of 62 articles of fair to good quality and comparable methods for vertebral fracture identification were considered. The prevalence of morphometric vertebral fractures in European women is highest in Scandinavia (26%) and lowest in Eastern Europe (18%). Prevalence rates in North America (NA) for White women ≥50 are 20-24%, with a White/Black ratio of 1.6. Rates in women ≥50 years in Latin America are overall lower than Europe and NA (11-19%). In Asia, rates in women above ≥65 are highest in Japan (24%), lowest in Indonesia (9%), and in the Middle East, Lebanon, rates are 20%. The highest-lowest ratio between countries, within and across continents, varied from 1.4-2.6. Incidence data is less abundant and more heterogeneous. Age-standardized rates in studies combining hospitalized and ambulatory vertebral fractures are highest in South Korea, USA, and Hong Kong and lowest in the UK. Neither a North-South gradient nor a relation to urbanization is evident. Conversely, the incidence of hospitalized vertebral fractures in European patients ≥50 shows a North-South gradient with 3-3.7-fold variability. In the USA, rates in Whites are approximately 4-fold higher than in Blacks. Vertebral fractures variation worldwide is lower than observed with hip fractures, and some of highest rates are unexpectedly from Asia. Better quality representative studies are needed. We investigate the occurrence of vertebral fractures, worldwide, using published data current until the present. Worldwide, the variation in vertebral fractures is lower than observed for hip fractures. Some of the highest rates are from North America and unexpectedly Asia. The highest-lowest ratio between countries, within and across continents, varied from 1.4-2.6. Better quality representative data is needed.

Ethnic difference of clinical vertebral fracture risk.

UNLABELLED: Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. This study observed that Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians, but the vertebral fracture rates were higher, resulting in a high vertebral-to-hip fracture ratio. As a result, estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate. INTRODUCTION: Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. The aim of this study was to report the incidence of clinical vertebral fractures among the Chinese and to compare the vertebral-to-hip fracture risk to other ethnic groups. METHODS: Four thousand, three hundred eighty-six community-dwelling Southern Chinese subjects (2,302 women and 1,810 men) aged 50 or above were recruited in the Hong Kong Osteoporosis Study since 1995. Baseline demographic characteristics and medical history were obtained. Subjects were followed annually for fracture outcomes with a structured questionnaire and verified by the computerized patient information system of the Hospital Authority of the Hong Kong Government. Only non-traumatic incident hip fractures and clinical vertebral fractures that received medical attention were included in the analysis. The incidence rates of clinical vertebral fractures and hip fractures were determined and compared to the published data of Swedish Caucasian and Japanese populations. RESULTS: The mean age at baseline was 62 ± 8.2 years for women and 68 ± 10.3 years for men. The average duration of follow-up was 4.0 ± 2.8 (range, 1 to 14) years for a total of 14,733 person-years for the whole cohort. The incidence rate for vertebral fracture was 194/100,000 person-years in men and 508/100,000 person-years in women, respectively. For subjects above the age of 65, the clinical vertebral fracture and hip fracture rates were 299/100,000 and 332/100,000 person-years, respectively, in men, and 594/100,000 and 379/100,000 person-years, respectively, in women. Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians. At the age of 65 or above, the hip fracture rates for Asian (Hong Kong Chinese and Japanese) men and women were less than half of that in Caucasians, but the vertebral fracture rate was higher in Asians, resulting in a high vertebral-to-hip fracture ratio. CONCLUSIONS: The incidences of vertebral and hip fractures, as well as the vertebral-to-hip fracture ratios vary in Asians and Caucasians. Estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate.

Interpretation and use of FRAX in clinical practice.

UNLABELLED: The introduction of the WHO FRAX® algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. Its use in fracture risk prediction has strengths, but also limitations of which the clinician should be aware and are the focus of this review INTRODUCTION: The International Osteoporosis Foundation (IOF) and the International Society for Clinical Densitometry (ISCD) appointed a joint Task Force to develop resource documents in order to make recommendations on how to improve FRAX and better inform clinicians who use FRAX. The Task Force met in November 2010 for 3 days to discuss these topics which form the focus of this review. METHODS: This study reviews the resource documents and joint position statements of ISCD and IOF. RESULTS: Details on the clinical risk factors currently used in FRAX are provided, and the reasons for the exclusion of others are provided. Recommendations are made for the development of surrogate models where country-specific FRAX models are not available. CONCLUSIONS: The wish list of clinicians for the modulation of FRAX is large, but in many instances, these wishes cannot presently be fulfilled; however, an explanation and understanding of the reasons may be helpful in translating the information provided by FRAX into clinical practice.

Bone density in Type 1 Gaucher disease.

Skeletal involvement is a major source of complications in patients with Type 1 Gaucher disease. To investigate the bone density and potential usefulness of bone densitometry in Gaucher disease, dual-energy X-ray absorptiometry was used to measure the density of the lumbar spine, femoral neck, trochanter, and distal radius in 61 adult patients ranging in age from 22 to 77 years. The mean bone density at each site was significantly lower than expected for age and sex. The severity of the osteopenia correlated significantly with other clinical indicators of disease severity, including the N370S/84GG genotype, prior splenectomy, and hepatomegaly. The bone density measurements also correlated significantly with the severity of skeletal disease as assessed by skeletal radiography. Vertebral density remained an independent predictor of the severity of bone involvement even after controlling for age, sex, weight, genotype, splenectomy, and hepatomegaly. These findings suggest that bone density measurements provide a quantitative assessment of bone involvement in Type 1 Gaucher disease, which may permit serial, noninvasive monitoring of bone changes in this progressive disorder.

Racial differences in pre- and postmenopausal bone homeostasis: association with bone density.

The disparity in fracture incidence and bone mass in women of European (white) and African (black) ancestry is of unknown etiology. To determine if racial differences in bone mass reflected racial differences in the mechanisms of bone turnover underlying bone mineral loss, we measured serum osteocalcin, serum alkaline phosphatase, fasting urinary calcium and hydroxyproline excretion, 24 h urinary excretion of calcium and sodium, and dietary intakes of calcium and vitamin D in 263 healthy pre-, peri-, and postmenopausal white and black women. In addition, radial and spinal bone density were measured cross-sectionally for comparison with biochemical measures of bone turnover. The biochemical parameters thought to reflect bone resorption (fasting urinary calcium and hydroxyproline excretions) were lower in black than in white women throughout the age and menopausal stages studied. The parameters thought to reflect bone formation (alkaline phosphatase and osteocalcin), were similar in the two racial groups among the premenopausal women, but osteocalcin was significantly lower among the peri- and postmenopausal blacks. Cross sectionally measured radial bone density increased with age in premenopausal black women, but it did not change with age in the white premenopausal subjects, a statistically significant difference. In peri- and postmenopausal women radial density declined significantly with years after menopause in both racial groups, but the rate of decline was significantly slower in the black women. Lumbar bone density in premenopausal white and black women did not change with age. After menopause lumbar bone density declined significantly and similarly in both racial groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Histomorphometric assessment of bone mass, structure, and remodeling: a comparison between healthy black and white premenopausal women.

While noninvasive studies of bone mass and turnover in blacks and whites abound, histologic evaluations are very rare. We have performed a comparative bone histomorphometric study of iliac biopsies from 55 healthy, premenopausal women including 21 blacks (mean age 33.4 + 1.2 years) and 34 whites (mean age 32.5 + 0.8 years) of comparable age, weight, body composition, education, and lifestyle. Biochemical indices of mineral metabolism: parathyroid hormone, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, serum ionized calcium, serum phosphorus, and urinary calcium/creatinine were measured in the fasting state. Blacks had lower 25-hydroxyvitamin D (315 +/- 3.36 vs. 63.21 +/- 3.79 nmol/l, p = 0.0001). Histomorphometric indices of bone volume, structure, and connectivity were not different between groups. The following indices of bone remodeling were also similar in both groups: eroded perimeter, osteoid width, mineralizing perimeter, tissue-based bone formation rate, osteoid maturation time, active formation period, and activation frequency. However, osteoid perimeter (black [B] = 15.85 +/- 1.30 vs. white [W] = 9.49 +/- 0.70%, p = 0.0002), osteoid area (B = 2.55 +/- 0.32 vs. W = 1.39 +/- 0.12%, p = 0.003), single-labeled perimeter (B = 5.46 +/- 0.54 vs. W = 4.04 +/- 0.33%, p = 0.03), mineralization lag time (B = 38.18 +/- 4.04 vs. W = 21.83 +/- 1.60 days, p < 0.009), and total formation period (B = 148.15 +/- 19.70 vs. W = 84.04 +/- 7.62 days, p = 0.0056) were higher in blacks than in whites. The quiescent perimeter (B = 76.91 +/- 1.40 vs. W = 84.25 +/- 0.91%, p = 0.0001), mineral apposition rate (B = 0.70 +/- 0.02 vs. W = 0.75 +/- 0.02 micron/day, p = 0.066), mineralizing osteoid perimeter (B = 0.49 +/- 0.04 vs. W = 0.75 +/- 0.04%, p = 0.0001) and adjusted apposition rate (B = 0.35 +/- 0.04 vs. W = 0.58 +/- 0.04 micron3/micron2/day, p = 0.0001) were all lower in blacks than in whites. These results indicate that there are no differences in bone volume, microstructure, or turnover between black and white premenopausal women. However, there are significant differences in the mechanism of bone formation between the two groups, with a lower rate of mineralized matrix apposition within each remodeling unit and a longer total formation period in blacks than in whites. The differences appear to the result of more frequent and/or longer inactive periods in the life span of the bone formation units in blacks. These differences may allow a greater overall deposition of bone mineral in black women and therefore help explain a higher bone mass and perhaps better bone quality in black than white women.

Resistance to bone resorbing effects of PTH in black women.

Black women have a lower incidence of vertebral and hip fractures than white women, possibly due to differences in skeletal and mineral metabolism. One suggested mechanism is that blacks have decreased skeletal sensitivity to parathyroid hormone (PTH). To test this hypothesis, we infused h(1-34)PTH in healthy premenopausal black (n = 15) and white (n = 18) women over 24 h and measured serum and urine indices of bone turnover and calcium metabolism throughout the infusion. At baseline, the mean 25-hydroxyvitamin D (25(OH)D) concentration was significantly lower in black women (46%). There were also nearly significant trends toward higher PTH and lower urinary calcium and pyridinoline levels in black women. During infusion, there were no racial differences in the mean (1-34)PTH levels achieved or in resultant elevations of serum calcium or 1,25-dihydroxyvitamin D (1,25(OH)2D) levels. Endogenous parathyroid suppression (measured by (1-84)PTH levels) was also similar between blacks and whites. There was an initial decline in urinary calcium/creatinine in both groups with a greater reduction in black women early in the infusion period (p < 0.05 at 8 h). Furthermore, blacks had lower levels of urinary calcium/creatinine throughout the infusion (p < 0.05 group difference). Bone formation markers (carboxy-terminal propeptide of type I procollagen and osteocalcin) decreased within 8 h and continued to decline throughout the infusion with no distinguishable racial differences (p < 0.05 time trend for both). The most dramatic difference between black and white women in response to PTH infusion was represented by the bone resorption markers. Three separate metabolites of bone resorption (cross-linked N-telopeptide of type I collagen, cross-linked C-telopeptide of type I collagen, and free pyridinoline) all showed substantially greater elevations in white (mean peak increments 399, 725, and 43%) compared with black women (mean peak increments 317, 369, and 17%) during the infusion (p < 0.05 group differences for all three variables). These data strongly suggest that blacks have decreased skeletal sensitivity to the acute resorptive effects of increased PTH. This finding indicates that calcium homeostasis may be accomplished in blacks (during times of relative calcium deficiency) by greater conservation of calcium from nonskeletal sources (most likely renal) with relative preservation of skeletal tissue. These differences in calcium economy could account, at least in part, for the increased bone mass and lower incidence of osteoporotic fractures in black women.

A prospective study of bone loss in African-American and white women--a clinical research center study.

Although bone loss occurs universally with age, the incidence of age-related osteoporotic fractures varies widely among ethnic groups. In the U.S., age-adjusted hip fracture incidence is 50% lower in African-American than in white women. Adult African-American women also have higher bone mass, but it is not known whether this difference is entirely due to higher peak bone mass or also results from slower rates of bone loss. Rates of bone loss were measured prospectively in 122 white and 121 African-American healthy, nonobese, pre- and postmenopausal women. Bone density was measured at 6-month intervals over a mean of 3-4 yr using single and dual photon absorptiometry of the forearm (cortical bone) and spine (trabecular bone). Similar rates of premenopausal bone loss were documented in both white and African-American women. However, in early menopause, bone loss was faster in the white women in the forearm (-2.4%/yr in whites vs. -1.2%/yr in African-Americans; P = 0.045), with a similar trend in the spine (-2.2%/yr in whites vs. -1.3/yr in African-Americans; P = 0.27). In women more than 5 yr postmenopause, the rates of bone loss did not differ by ethnic group. Our results indicate that the higher bone mass in African-American women is largely due to the attainment of a greater peak bone mass by early adulthood. However, slower rates of bone loss in the early postmenopausal period may also contribute to the higher bone density of older African-American women. Although bone loss occurs in both groups, there are ethnic differences in bone loss rates which indicate that data derived from white women cannot be simply extrapolated to nonwhite populations. Ethnic group-specific data on the determinants of bone homeostasis are needed.

Immunoreactive corticotropin-releasing factor is present in human maternal plasma during the third trimester of pregnancy.

Immunoreactive (IR) corticotropin-releasing factor (CRF)-like activity was detectable in the majority of plasma samples obtained from women in the third trimester of pregnancy (68.7 +/- 23.6 pg/ml (14.4 +/- 4.9 fmol/ml); mean +/- SE, n = 15), but not in plasma (less than 10 pg/ml) from first (n = 9) or second (n = 11) trimester of pregnancy, 1 day post partum (n = 7), non-pregnant women (n = 10), or in plasma obtained from patients with Cushing's disease (n = 2) or Nelson's syndrome (n = 1), or in basal (n = 6) or ether-stressed (n = 6) rat plasma. Gel filtration of third trimester pooled plasma revealed that the majority of such material eluted with Kav of rat CRF (1-41). The IR CRF (1-41)-sized material eluted with the identical retention time as rat CRF in a reverse phase high performance liquid chromatography (HPLC) system. The detection of IR CRF exclusively in third trimester maternal plasma, together with our previous demonstration that material physicochemically indistinguishable from it is present in human term placental extracts, suggests that the placenta may be the source of plasma IR CRF.

Calcium, vitamin D, and parathyroid hormone status in young white and black women: association with racial differences in bone mass.

The etiology of the racial disparity in bone mass and fracture rate is unknown. Since the PTH-vitamin D endocrine system is a major regulator of calcium metabolism and bone turnover, this cross-sectional study examined the relationship of radial and lumbar bone density to vitamin D metabolite and PTH concentrations and to calcium intake and excretion in 67 white and 70 black highly comparable, healthy, premenopausal women. Bone density at both radial and lumbar sites was higher in blacks than in whites. Serum 25-hydroxyvitamin D was slightly but not statistically significantly (P = 0.08), lower in blacks than in whites, but there were no racial differences in 1,25-dihydroxyvitamin D, PTH, or renal tubular maximum for reabsorption of phosphate. The mean 25-hydroxyvitamin D concentration in blacks was well within the normal range and was not associated with evidence of secondary hyperparathyroidism. There were no correlations of bone density to vitamin D or PTH concentrations. Although there were no racial differences in dietary intake of calcium and vitamin D or in sodium excretion, 24-h urinary calcium excretion was significantly lower in blacks than in whites, and calcium excretion was inversely associated with radial bone density. In contrast to previous reports, in healthy, normal weight, premenopausal black women there is no evidence of vitamin D deficiency or secondary hyperparathyroidism, suggesting that factors other than the vitamin D-PTH axis are responsible for racial differences in bone mass.

Radial and vertebral bone density in white and black women: evidence for racial differences in premenopausal bone homeostasis.

The reasons for a different incidence of osteoporotic fractures in white and black women are unknown. Previous racial comparisons of bone mass have been limited by racial differences in body weight and socioeconomic, health, and nutritional status. This cross-sectional study examined bone density in 105 black and 114 white healthy nonobese women, 24-65 yr old, using dual photon absorptiometry of the lumbar spine and single photon absorptiometry of the distal radius. Bone density at both sites was higher in blacks at all ages than in whites. When adjusted for age and body mass index, mean bone density was 6.5% higher in blacks at both spine and radius (P less than 0.0001). The cross-sectional rate of decline of vertebral bone density was similar between races; however, radial density increased 3.8%/decade (P = 0.03) in premenopausal blacks under age 46 yr, while it declined 3.2%/decade (P = 0.09) in premenopausal whites. The racial difference in slopes in these premenopausal women is significant (P = 0.002). These findings suggest that attainment of higher peak bone mass and delayed onset of bone loss contribute to the lower incidence of osteoporotic fractures in black women.

A peptide from the adenovirus fiber shaft forms amyloid-type fibrils.

The fiber protein of adenovirus consists of a C-terminal globular head, a shaft and a short N-terminal tail. The crystal structure of a stable domain comprising the head plus a part of the shaft of human adenovirus type 2 fiber has recently been solved at 2.4 A resolution [van Raaij et al. (1999) Nature 401, 935-938]. A peptide corresponding to the portion of the shaft immediately adjacent to the head (residues 355-396) has been synthesized chemically. The peptide failed to assemble correctly and instead formed amyloid-type fibrils as assessed by electron microscopy, Congo red binding and X-ray diffraction. Peptides corresponding to the fiber shaft could provide a model system to study mechanisms of amyloid fibril formation.

Effect of source strength and attenuation on dual photon absorptiometry.

A systematic error in dual photon absorptiometry (DPA) measurements of bone mineral density (BMD) related to source strength has been previously described and attributed to an erroneous algorithm for deadtime correction. Since detected counts (or photon flux) is a product of source strength and attenuation, the effect of various source activities and attenuation depths on BMD calculations were evaluated using a phantom. Ten DPA scans were acquired at two source strengths, 0.3 and 1.0 Ci, and at each of two water depths, 16.4 and 24.5 cm. These activities and depths are within the range encountered clinically. Scans were acquired and processed using a commercially available lumbar spine scanner and software, and were reanalyzed with two upgraded versions of software. Mean BMD obtained with the initial software varied by 2 to 14% with changes in both sources strength and attenuating depth. Software revisions reduced but did not entirely eliminate these differences. The remaining 6% discrepancy is of sufficient magnitude to influence both patient management and research investigations.

Low body weight as a risk factor for hip fracture in both black and white women.

A lower incidence of hip fracture in black women has been reported by several studies. The most frequently proposed explanations for this phenomenon have included a genetically greater bone mass, better preservation of bone due to the fact that certain populations of black women perform more physical labor, and the impact of other unidentified environmental and/or lifestyle factors. This retrospective study demonstrates that low body weight is as significant a risk factor for hip fracture in black women as it is in white women. Coupled with the known higher prevalence of obesity in the older black female population, the findings of this study suggest that differences in body weight may be a significant and possibly sufficient explanation for the lower incidence of hip fracture in black women.

Osteoporosis. Recommended guidelines and New Jersey legislation.

More than 28 million Americans aged 50 and over have osteoporosis or low bone density. While 80% of those affected are women, one in eight men also suffer from the disease. This number is expected to increase as men live longer. Commonly called the "silent disease," osteoporosis exhibits no symptoms or pain until a fracture occurs. The most common fractures involve the wrist, vertebra, and hip. Half of all women and 20% of men will have at least one osteoporosis fracture in their lifetime. This article describes statewide efforts to prevent and manage osteoporosis and the recommended practice guidelines for the diagnosis and treatment of the disease.

Use of single-cysteine mutants to probe the location of the disulfide bond in LamB protein from Escherichia coli.

The two cysteine residues of the LamB protein of Escherichia coli outer membrane have been shown to form an intrasubunit disulfide whose location differs greatly in the two current topology models of the LamB protein. This study probes the location of the disulfide by examining conditions for intersubunit disulfide formation in single-cysteine mutants of LamB protein. Formation of an intersubunit bond in the purified mutant proteins, which resulted in a disulfide-linked dimer, only occurred after heat treatment, suggesting the disulfide is not exposed on the surface in the native protein.

Purification and functional characterization of mutant LamB proteins.

The phage lambda receptor, or LamB, proteins have been purified from several missense lamB mutants, and the properties of the channel produced by these proteins were investigated in a reconstituted liposome system. In at least one mutant, a significant reduction in the sugar selectivity of the channel was observed, and another mutant protein interacted poorly with the maltose-binding protein immobilized on Sepharose beads.

Specificity of diffusion channels produced by lambda phage receptor protein of Escherichia coli.

The lamB protein, the receptor for phage lambda, was purified from the outer membrane of Escherichia coli K-12 by extraction with Triton X-100 and EDTA, chromatography on DEAE-Sephacel in Triton X-100, exchange of Triton for cholate by gel filtration, and chromatography on Sephacryl S-200 in cholate, NaCl, and EDTA. The purified protein appeared to exist as several oligomeric species. In an equilibrium retention assay with reconstituted vesicles containing phospholipids and lipopolysaccharide, the lamB protein conferred permeability for disaccharides. In a liposome swelling assay designed to measure rates of diffusion, the lamB protein conferred permeability to phospholipid liposomes for a variety of substrates. The rates obtained indicate the permeation facilitated by the lamB protein is specific, discriminating among substrates by both size and configuration. For example, maltose diffused into liposomes 40 times faster than sucrose, about 8 times faster than cellobiose, and about 12 times faster than maltoheptaose. The results suggest that the lamB protein forms a transmembrane channel containing a site (or sites) that loosely interacts with the solutes.

Bacteriophage lambda receptor protein in Escherichia coli K-12: lowered affinity of some mutant proteins for maltose-binding protein in vitro.

Mutant and wild-type LamB proteins (phage lambda receptor proteins) were purified by affinity chromatography with immobilized maltose-binding protein, and their transport functions were tested in reconstituted liposomes. Two mutant proteins exhibited a marked decrease in affinity for immobilized maltose-binding protein, as well as altered transport rates.