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Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor family, is a potent inhibitor of osteoclast activation and differentiation. In animal models OPG prevents bone loss, and in humans bone resorption can be reduced by injections of OPG. OPG may also play a role in cardiovascular disease since mice lacking the OPG gene display arterial calcification. In a screening effort of the OPG gene, we recently discovered a single nucleotide polymorphism in the promoter region of OPG (T950C), and reported an association with vascular morphology and function in 59 healthy individuals. Due to the pronounced effect of OPG on bone turnover, the present study was conducted to investigate whether OPG polymorphisms are also associated with bone mineral density or with fracture. The relationship between single nucleotide polymorphisms in the promoter region of OPG (T950C) and the first intron (C1217T), and bone mineral density, measured by DXA in the hip or spine or ultrasound of the heel, was investigated in the Malmö OPRA-study of 1044 women, all 75 years old. The possible relation to fracture incidence was also analyzed. Among the 858 and 864 individuals respectively, genotyped, no significant associations between the investigated single nucleotide polymorphisms and bone mineral density measurements (T950C P = 0.50–0.64, C1217T P = 0.51–1.00), quantitative ultrasound measurements of the calcaneus, or fractures (T950C P = 0.61–0.66, C1217T P = 0.14–0.33) were found. Thus, our results show that polymorphisms in the OPG gene, one of which has previously been found to be associated with cardiovascular morphology and function, are not associated with bone mineral density in elderly Swedish women. [ABSTRACT FROM AUTHOR]

Background: Earlier studies have shown that physical exercise and a higher workload increase muscle strength and improve gait and balance at all ages for both sexes. Published studies have, so far, failed to investigate the functional performance of elderly individuals concerning their long-term physical activity and variables of daily living.Objective: To compare elderly women who participate in long-term, moderate exercise programmes with two age-matched groups of women from an urban and a rural community.Methods: All participants answered a questionnaire about health, social circumstances and fractures. We measured the vibration threshold of the lower extremities, bone mineral density of the distal radius and functional performance such as muscle strength, balance and gait.Results: The elderly, active groups performed significantly better in all functional tests and had sustained fewer fractures than the urban control group. When the comparison was made with the rural control group the differences were less obvious. The active group rated their health as better than both the control groups.Conclusion: Elderly women, who continue with moderate exercise programmes over many years, sustain fewer fractures and have better muscle strength, balance, gait and health ratings than women in general. Whether this is the result of the exercise or inherited characters, remains to be proved. [ABSTRACT FROM AUTHOR]

Hip fracture is one of the most severe consequences of osteoporosis affecting aged women. However, abnormalities of bone turnover responsible for bone loss in this condition have not been clearly defined. To further evaluate the bone metabolic status of women sustaining hip fracture, we have prospectively measured serum osteocalcin as a marker of bone formation and urinary excretion of pyridinoline (Pyr) and deoxypyridinoline (D-pyr) cross-links as markers of bone collagen degradation in 174 independently living women (80 +/- 8 years) within a few hours after a hip fracture. Comparison was made with 77 age-matched controls (80 +/- 5 years) and 17 premenopausal women (39 +/- 3 years). In addition 15 of the patients were followed with daily measurements during the first postoperative week. At the time of admission osteocalcin was 20% lower in the fractured women compared to the elderly controls (7.6 +/- 3.8 vs. 9.5 +/- 4.5 ng/ml, P = 0.001). Pyr and D-pyr were 36% and 40% higher, respectively (P = 0.0001), than in elderly controls and 85% and 76% higher than in premenopausal controls (P = 0.0001). Serum osteocalcin did not correlate with the cortisol level measured at the same time (r = 0.03, ns), nor with serum albumin and creatinine. Serum osteocalcin remained unchanged within 18 hours after fracture, whereafter it progressively decreased until the third postoperative day. No correlation was noted between the excretion of pyridinoline cross-links and the time elapsed from fracture.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to evaluate the bone turnover by using bone metabolic markers in relation to previous fracture history and independent of bone mass. Patients and controls were recruited from a population-based study of 193 women, all living in the same city and aged 60, 70, and 80 years. The bone mineral content (BMC) was measured bilaterally in the distal forearm by single-photon absorptiometry (SPA). At the same time, serum samples were obtained for biochemical analysis. Of the 193 women, we identified 26 with at least one major fracture during the past few years. Each of these 26 women with a certified recent previous fracture was individually matched with a woman from the same study group of equal BMC and age but without a fracture history. In the two groups, the serum samples were analyzed for osteocalcin, C-terminal procollagen peptide (P1CP), alkaline phosphatase, bone-specific alkaline phosphatase, calcium, phosphate, and albumin. The serum concentration of osteocalcin was 20% lower in the women with a previous fracture than in the controls (P = 0.03). The other markers of bone formation gave similar values in the two groups. There was a significant correlation between the osteocalcin and P1CP concentrations (P = 0.001). Our findings indicate that the susceptibility to fractures independent of factors such as age and BMC may be related to a decreased bone turnover. [ABSTRACT FROM AUTHOR]

The effect of intense physical training on the bone mineral content (BMC) and soft tissue composition, and the development of these values after cessation of the active career, was studied in 40 nationally or internationally ranked male weight lifters. Nineteen were active and 21 had retired from competition sports. Fifty-two age- and sex-matched nonweight lifters served as controls. The bone mineral density (BMD) in total body, spine, hip, and proximal tibial metaphysis was measured with a Lunar Dual-energy X-ray absorptiometry (DXA) apparatus and the BMD of the distal forearm was measured with single photon absorptiometry (SPA). Seventeen of the lifters had been measured earlier with SPA in the forearm and 23 in the tibial condyle during their active career in 1975. The BMD was significantly higher in the weight lifters compared with the controls (10% in the total body P < 0.001, 12% in the trochanteric region P < 0.001, and 13% in the lumbar spine P < 0.001). All measured regions except the head showed significant higher bone mass in the weight lifters compared with the controls. In older lifters, the difference from the controls seemed to increase in total body and lumbar vertebrae (BMD), but remained unchanged in the hip. Significant correlation was found between the SPA measurements in 1975 and the corresponding measurements 15 years later in both the forearm (r = 0.51, P < 0.05 at the 1-cm level and r = 0.87, P < 0.001 at the 6-cm level) and in the tibial condyle (r = 0.61, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

With electron probe microanalysis the concentration of calcium and phosphorus was determined in central parts of tibia epiphyseal bone. Trabeculae from five men who had had a fracture of the ipsilateral tibia diaphysis were analyzed. The results were compared with those of five men who had suffered sudden death. There was an even distribution of calcium in the control cases: the mean value was 45 +/- 1 wt%. In the posttraumatic group of patients there was a lower mean and a greater scatter: 29 +/- 10 wt%. Also, the concentration of phosphorus was lower in the posttraumatic cases as compared with the cadavers. [ABSTRACT FROM AUTHOR]

This retrospective case control study was done in order to investigate whether patients who sustain a "nonosteoporotic fracture" early in life also continue to sustain fragility fractures later in life. All patients who had been treated at the Department of Orthopedics in Malmö with a tibial shaft fracture from 1949 to 1963 (n = 767) or an ankle fracture from 1961 to 1965 (n = 786) were included in this study. At the time of follow-up in 1992, 231 of the patients who sustained a tibial shaft fracture and 260 of the patients who sustained an ankle fracture were still living in the city of Malmö. Objective registration was done of all subsequent fractures that these former patients had sustained. Comparison was done with corresponding data from double numbers of age- and sex-matched controls who at that time (1950s and 1960s) had no such fractures. At the time of the fracture as well as today, the controls were living in the area of Malmö. Individuals with earlier tibial or ankle fractures had an increased incidence of fractures generally classified as fragility fractures. There was no difference in this respect between men and women, nor whether the initial fracture had been diaphyseal or metaphyseal. We conclude that sustenance of fractures early in life may serve as a predictor for fragility fractures later in life. [ABSTRACT FROM AUTHOR]

The concentrations of calcium and phosphorus were determined in central parts of bone trabeculae in the human iliac crest by means of an energy dispersive microanalysis technique. Two age groups, each consisting of six suddenly diseased male subjects, were investigated. It was found that the concentrations of calcium and phosphorus did not differ between young and old men. The obtained mean values were fairly alike and determined to 40 and 17 weight %, respectively. [ABSTRACT FROM AUTHOR]

In order to find out whether the concentration of bone gla-protein (BGP) is elevated in blood derived directly from bone tissue compared to peripherically sampled blood a peroperative model was used. Blood was collected simultaneously from an armvein and from the osteotomized surface of the bone during total hip replacement in 18 patients. Peripheral blood was also collected before the anaesthetic procedure. The anaesthetic and/or the operative procedure slightly decreased the level of BGP in the peripheral blood during this short time interval, but serum BGP was not different in the bone - marrow derived blood and in the peripheral blood taken simultaneously. These data suggest that BGP released from bone into the circulation is rapidly cleared from the marrow and that peripheral serum BGP is a valid index of the bone-derived levels of BGP. [ABSTRACT FROM AUTHOR]

Introduction: Parathyroid hormone (PTH) is a key regulator of calcium metabolism. Parathyroid hormone-like hormone (PTHrP) contributes to skeletal development through regulation of chondrocyte proliferation and differentiation during early bone growth. Both PTH and PTHrP act through the same receptor (PTHR1). A second receptor, PTHR2, has been identified although its function is comparatively unknown. PTH hyper-secretion induces bone resorption, whereas intermittent injection of PTH increases bone mass. To explore the effects of genetic variation in the PTH pathway, we have analysed variations in PTH, PTHLH, PTHR1 and PTHR2 in relation to bone mass and fracture incidence in elderly women., Materials and Methods: This study includes 1044 elderly women, all 75 years old, from the Malmö Osteoporosis Prospective Risk Assessment study (OPRA). Single nucleotide polymorphisms (SNPs) from 4 genes and derived haplotypes in the PTH signaling pathway were analysed in 745-1005 women; 6 SNPs in the PTH gene and 3 SNPs each in the PTHLH, PTHR1 and PTHR2 genes were investigated in relation to BMD (assessed at baseline), fracture (434 prevalent fractures of all types over lifetime, self-reported and 174 incident fractures up to 7 years, X-ray verified) and serum PTH., Results and Conclusion: Individually, SNPs in the 4 loci did not show any significant association with BMD. Neither were PTHLH, PTHR1 and PTHR2 polymorphisms associated with fracture. Three of 5 common haplotypes, accounting for >98% of alleles at the PTH locus, were identified as independent predictors of fracture. Haplotype 9 (19%) was suggestive of an association with fractures of any type sustained during lifetime (p=0.018), with carriers of one or more copies of the haplotype having the lowest incidence (p=0.006). Haplotypes 1 (13%) and 5 (37%) and 9 were suggestive of an association with fractures sustained between 50 and 75 years (p=0.02, p=0.013 and p=0.034). Carriers of haplotypes 1 and 5 were more likely to suffer a fracture (haplotype 1, p=0.045; haplotype 5, p=0.008). We conclude, that while further genotyping across the gene is recommended, in this cohort of elderly Swedish women, polymorphisms in PTH may contribute to the risk of fracture through mechanisms that are independent of BMD.