Bone turnover markers are correlated with quantitative ultrasound of the calcaneus: 5-year longitudinal data.

SUMMARY: Associations between bone turnover markers and calcaneal ultrasound (quantitative ultrasound, QUS) were studied in a population-based sample of 810 elderly women. Baseline bone turnover markers correlated with baseline QUS as well as with 5-year prospective changes in QUS. INTRODUCTION: Bone turnover markers are associated with areal bone mineral density, but the knowledge on the association with QUS is limited. METHODS: Eight hundred ten women, all 75 years old, were investigated at baseline. Five hundred six completed a 5-year follow-up. Bone turnover markers and calcaneal QUS [speed of sound (SoS), broadband ultrasound attenuation (BUA), stiffness] were investigated at baseline. QUS was investigated at follow-up. RESULTS: All bone turnover markers were correlated with baseline QUS [standardized regression (Beta(std)) values from -0.07, p < 0.05 to -0.23, p < 0.001], with the exception of bone-specific alkaline phosphatase (S-Bone ALP) which was not correlated with BUA and stiffness index. When the correlations between baseline bone turnover markers and 5-year changes in QUS were analyzed, three serum osteocalcins were correlated with changes of SoS and stiffness index (Beta(std) = -0.11, p < 0.05 to -0.17, p < 0.001). Also S-CTX-I correlated with changes of SoS and stiffness index (Beta(std) = -0.10 and -0.09, respectively, p < 0.05). S-TRACP5b, urinary deoxypyridinoline/crea, and U-MidOC/crea correlated with changes of SoS (Beta(std) = -0.10 and p < 0.05 for all). S-Bone ALP did not correlate with change of QUS. None of the bone turnover markers correlated with changes of BUA. CONCLUSIONS: Bone turnover markers correlate with concomitantly assessed QUS as well as with longitudinal change in QUS.

Genetic variation in the PTH pathway and bone phenotypes in elderly women: evaluation of PTH, PTHLH, PTHR1 and PTHR2 genes.

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.

Prediction of bone loss using biochemical markers of bone turnover.

UNLABELLED: The association between baseline levels of eleven bone turnover markers and 5-year rate of bone density change was prospectively studied in a population-based sample of 601 75-year-old women. Several bone formation and resorption markers as well as urinary osteocalcin were modestly correlated to rate of bone density change. INTRODUCTION: Prediction of bone loss by bone turnover markers (BTMs) has been investigated with conflicting results. There is limited information in the elderly. METHODS: Eleven bone turnover markers were analyzed in 75-year old women in the OPRA study (n = 601) and compared to the 5-year change of areal bone mineral density (aBMD) in seven skeletal regions. RESULTS: Annual aBMD change varied between +0.4% (spine) and -2.0% (femoral neck). Significant associations (p < 0.01) were found for four different serum osteocalcins (S-OCs) (standardized regression coefficient -0.20 to -0.22), urinary deoxypyridinoline (-0.19), serum TRACP5b (-0.19), serum CTX-I (-0.21), two of the three urinary osteocalcins (U-OCs) (-0.16) and aBMD change of the leg region (derived from the total body measurement). After adjustment for baseline aBMD, associations were found for all S-OCs (-0.11 to -0.16), two of the three U-OCs (-0.14 to -0.16) and aBMD change at the total hip, and for three of the four S-OCs (-0.14 to -0.15), S-TRACP5b (-0.11), two of the three U-OCs (-0.14 to -0.15) and aBMD change at the femoral neck. There were no significant results concerning aBMD change at the spine. CONCLUSION: This study indicates that BTMs are correlated with aBMD loss in some skeletal regions in elderly women.

Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women.

Vitamin D supplements have been used to prevent fractures. The effect may be mediated through increased bone mass, but also through reduced falling propensity. The aim of this study was to evaluate the association between 25-hydroxy vitamin D levels (25OHD), fall-associated variables (including tests of functional performance), and fracture in ambulatory women. At baseline 25OHD was measured in 986 women. Fall-associated variables were investigated at baseline. Fractures were recorded during a 3-year follow-up. Four percent of the women had 25OHD levels below 20 ng/ml (50 nmol/l), and 26% had 25OHD levels below 30 ng/ml (75 nmol/l). 25OHD correlated with gait speed (r =0.17, P <0.001), the Romberg balance test (r =0.14, P <0.001), self-estimated activity level (r =0.15, P <0.001), and thigh muscle strength (r =0.08, P =0.02). During the 3-year follow-up, 119 out of the 986 women sustained at least one fracture. The Cox proportional hazard ratio (HR) (95% confidence interval) for sustaining a fracture during the follow-up was 2.04 (1.04-4.04) for the group of women with 25OHD below 20 ng/ml, in which 9 out of 43 women sustained a fracture. Thirty-two of the 256 women with 25OHD levels below 30 ng/ml sustained a fracture during the follow-up, with a non-significant HR of 1.07 (1.07-1.61). This cohort of elderly, ambulatory women had a high mean 25OHD. A low 25OHD was associated with inferior physical activity level, gait speed and balance. A 25OHD level below 30 ng/ml was not associated with an increased risk of fractures in this study. However, a subgroup of women with 25OHD levels below 20 ng/ml had a tendency to an increased risk of fractures, which may be associated with an inferior physical activity and postural stability.

Single nucleotide polymorphisms in the human gene for osteoprotegerin are not related to bone mineral density or fracture in elderly women.

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.

Bone turnover responses to changed physical activity.

The aim of the study was to compare bone turnover in male soccer players with controls and to follow bone turnover with changes in activity level. Serum-osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP) and total alkaline phosphatases (tALP) were measured to assess bone formation. Bone resorption was detected by carboxyterminal cross-linked telopeptide of type I collagen (ICTP). Bone turnover of 12 male premier league soccer players (mean age 23 years, range, 17-34) exercising 12 hours/week (range, 8-15) were at the last day of the soccer season compared with 27 age- and gender-matched controls. Bone turnover was followed weekly during a 4-week resting period between two seasons, and a further 10 days following resumption of full training. Data are presented as mean +/- SEM. Both OC (22 +/- 12%) and ICTP (34 +/- 17%) were higher in the players compared with the controls at the end of the season (both P < 0.05, respectively). After 2 weeks of reduced physical activity among the athletes, the PICP levels were 21 +/- 4% (P < 0.05) lower and the ICTP levels 8 +/- 12% higher (P = 0.07) compared with baseline. OC, PICP, and tALP was then no different compared with controls and ICTP was higher than controls (P < 0.001). Ten days within the new season, there was a 23 +/- 5% increase in PICP (P < 0.001) and a 4 +/- 4% decrease in ICTP (P < 0.05) compared with the end of the resting period. In summary, male soccer players have higher bone turnover compared with age- and gender-matched controls. Changes in physical activity level were associated with changes in bone formation and resorption as evaluated by bone markers within weeks, and after 2 weeks rest, ICTP was higher in the athletes than the controls. We conclude that the higher age-related diminution in BMD, previously reported in former soccer players compared with age- and gender-matched controls, may be the result of increased bone resorption, evaluated by ICTP, compared with the controls.

Influence of muscle strength, physical activity and weight on bone mass in a population-based sample of 1004 elderly women.

High physical activity level has been associated with high bone mass and low fracture risk and is therefore recommended to reduce fractures in old age. The aim of this study was to estimate the effect of potentially modifiable variables, such as physical activity, muscle strength, muscle mass and weight, on bone mass in elderly women. The influence of isometric thigh muscle strength, self-estimated activity level, body composition and weight on bone mineral density (dual energy X-ray absorptiometry; DXA) in total body, hip and spine was investigated. Subjects were 1004 women, all 75 years old, taking part in the Malmö Osteoporosis Prospective Risk Assessment (OPRA) study. Physical activity and muscle strength accounted for 1-6% of the variability in bone mass, whereas weight, and its closely associated variables lean mass and fat mass, to a much greater extent explained the bone mass variability. We found current body weight to be the variable with the most substantial influence on the total variability in bone mass (15-32% depending on skeletal site) in a forward stepwise regression model. Our findings suggest that in elderly women, the major fracture-preventive effect of physical activity is unlikely to be mediated through increased bone mass. Retaining or even increasing body weight is likely to be beneficial to the skeleton, but an excess body weight increase may have negative effects on health. Nevertheless, training in elderly women may have advantages by improving balance, co-ordination and mobility and therefore decreasing the risk of fractures.

Effect of previous and present physical activity on bone mass in elderly women.

The importance of a physically active lifestyle as a preventive measure for maintaining bone mass is often stressed. The aim of this study was to evaluate the effect of everyday physical activity on bone mass from young adulthood to old age in 75-year-old women. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry technique in total body, hip (femoral neck and trochanter), and spine (LII-LIV) in a population-based cohort of 995 women, all 75 years old. Each woman responded to a questionnaire giving an estimate of the previous and present physical activity level at work and leisure time from youth and up to the present age of 75 years. No correlations were found between the different estimates of physical activity level and BMD. In a multiple regression analysis the different estimates of physical activity level did not have any combined effect on BMD in any of the skeletal regions measured; neither did the physical activity, previous or present, differ when the subgroup of women with a BMD in the highest quintile at all sites was compared with women with a BMD in the lowest quintile. The activity level in the various areas of life did not correlate to each other indicating that few women had chosen a generally active vs non-active lifestyle. A hypothetical positive effect on bone by one activity could therefore be diminished by another. The answer alternatives were mostly not normally distributed, which could also affect the results, making it difficult to identify women with extremely high or low physical activity level. In conclusion, the results from this study of randomly selected elderly women cannot confirm an effect of previous and present everyday physical activity on bone mass. Neither was it possible to find an effect of physical activity in those women with the highest BMD at all sites, suggesting that other factors are of greater importance for maintaining bone mass in elderly women.

Effects of cigarette-smoking on bone mass as assessed by dual-energy X-ray absorptiometry and ultrasound.

In order to elucidate the influence of nicotine smoking on bone mass in elderly women, bone mass was cross-sectionally assessed by dual energy X-ray absorptiometry (DXA) in total body, hip and lumbar spine, as well as with ultrasound of calcaneus and phalanges of the hand. Subjects were 1,042, 75-year old women, recruited on a population basis (Osteoporosis Prospective Risk Assessment (OPRA) study). We found bone mineral density (BMD) to be lower in hip (0.71 vs. 0.76 g/cm2, p<0.0001 for femoral neck) and total body (0.96 vs. 1.02 g/cm2, p<0.0001) in current smokers compared to never-smokers. There was no difference in BMD of the lumbar spine between current smokers and never-smokers. Bone mass as assessed by ultrasound of the calcaneus was lower for speed of sound ( p<0.01), broadband ultrasound attenuation ( p<0.0001) and stiffness ( p<0.0001) in current smokers than in never-smokers. No differences were found for ultrasound measurements of the phalanges between smokers and never-smokers. Also, weight and current physical activity as assessed by a questionnaire differed significantly between current smokers and never-smokers. There was no evident difference between former smokers and never-smokers in any of the skeletal regions assessed by DXA or ultrasound. After correcting for differences in weight and physical activity, current smokers had lower BMD in all hip sites ( p<0.05) and total body ( p<0.01) compared to never-smokers. Ultrasound and BMD spine did not differ between these two groups after correction for weight and physical activity. We conclude that nicotine smoking has a negative influence on bone mass independent of differences in weight and physical activity. This difference is detected by DXA but not by ultrasound measurements of the calcaneus or the phalanges. The present data are encouraging since no bone mass differences were found between former and never-smokers.

Histology of impacted bone-graft incorporation.

We describe the histologic findings of 31 tissue samples from 21 cases in 19 different patients taken 1 to 48 months after revision arthroplasty and impaction grafting in the hip (Lubinus SP-II prosthesis Waldemar Link, Hamburg, Germany, or Charnley Elite prosthesis, Johnson & Johnson, New Brunswick, NJ) and the knee (Link Rotation Knee Waldemar Link). One month after surgery, a fibrous stroma and some newly formed woven bone were found in the graft bed. After 4 months, many of the dead trabeculae in the graft bed had layers of living bone and osteoid in all samples. These layers, indicating a gradual ingrowth of living bone, increased over time. In the proximal end of the femur examined after 48 months, a significant proportion of the graft bone remained dead, whereas in the rest of the femur, the bone healing was complete. A similar but possibly less frequent bone formation was found in the 2 cases evaluated after a revision total knee arthroplasty combined with impaction grafting.

Pregnancy and lactation confer reversible bone loss in humans.

The influence of pregnancy on bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DXA) in 73 women (mean age 29 years, range 20-44 years) postpartum. Fifty-five age-matched women served as controls. The influence of lactation was evaluated in 65 of the delivered women who were followed with repeated measurements, a mean of 4.5 +/- 0.1 and 11.5 +/- 0.1 months after the delivery. The influence of multiple pregnancies was evaluated in 39 premenopausal women (mean age 38 years, range 31-54 years) with a minimum of four pregnancies (range 4-7). Fifty-eight age-matched healthy premenopausal women with a maximum of two pregnancies (range 0-2) served as controls. Data are presented as mean +/- SEM. BMD data are adjusted for differences in total fat mass and total lean mass. Lumbar spine BMD was 7.6 +/- 0.1% and total body BMD 3.9 +/- 0.1% lower in women postpartum compared with controls (both p<0.001). BMD did not decrease significantly in non-breastfeeding mothers. Mothers breastfeeding for 1-6 months decreased femoral neck BMD by 2.0 +/- 1.0% during the first 5 months postpartum (p<0.001). No further BMD loss was seen between 5 and 12 months postpartum. Femoral neck BMD 12 months after delivery was 1.3 +/- 0.8% lower than after delivery in mothers breastfeeding for 1-6 months (p = 0.05). Mothers breastfeeding for more than 6 months decreased Ward's triangle BMD by 8.5 +/- 1.0% and lumbar spine BMD by 4.1 +/- 0.8% during the first 5 months postpartum (both p<0.05). No further BMD loss was seen between 5 and 12 months postpartum. Femoral neck BMD 12 months after delivery was 4.0 +/- 1.1% lower and Ward's triangle BMD 5.3 +/- 1.9% lower than after delivery in mothers breastfeeding for more than 6 months (both p<0.05). BMD loss was higher during the first 5 months following delivery in the lactating women compared with the non-lactating women (p<0.05 comparing lumbar spine BMD loss in lactating mothers versus non-lactating mothers). However, in women with a minimum of four pregnancies the BMD was no lower than in age-matched women with fewer pregnancies. Total duration of lactation was not correlated with the present BMD. In summary, pregnancy seem to confer a low BMD with additional BMD loss during 5 months of lactation. Even if complete restoration in BMD was not reached within 5 months of weaning, women with four pregnancies or more had a BMD no lower than women with two pregnancies or fewer. We conclude that neither an extended lactation period nor multiple pregnancies could be used as a risk factor when predicting women at risk for future osteoporosis.

Vitamin D deficiency and ovariectomy reduced the strength of the femoral neck in rats.

Vitamin D (vit D) deficiency is common in the elderly, and the aim of this study was to investigate whether vit D deprivation in ovariectomized (ovx) and normal rats would reduce fracture strength. Forty mature female Wistar rats were randomized into four groups: two were ovariectomized (ovx) and two were sham-operated (sham). One ovx and one sham group were fed a vit D-deficient diet (Ovx-D and Sham-D), and the control groups were fed normal rat chow (Ovx and Sham) for 12 weeks. Vit D deficiency was substantiated after 12 weeks by undetectable serum concentrations of 25OHD in the Sham-D and Ovx-D groups. 85Sr activity was lower in Sham-D than in the other groups (P < 0.005). Tibial and femoral weights and lengths showed no differences. Distal tibial trabecular bone volume was reduced in both ovx groups compare with sham (P < 0.005). Bone mineral density (BMD) was higher in sham than in Sham-D and both ovx groups (P < 0.005). Femoral area moment of inertia increased and ultimate stress decreased in Ovx-D compared with ovx (P < 0.05). Other biomechanical properties of the femoral shafts did not differ significantly. The femoral neck was significantly weaker in Ovx-D than in the other groups. In conclusion, ovx decreased tibial trabecular bone volume and both ovx and vit D depletion reduced femoral BMD in rats. Vit D depletion reduced the ultimate stress in the femoral shaft, and the combined depletion of estrogen and vit D significantly reduced the fracture strength in the femoral neck. This fits well with clinical evidence of how postmenopausal status combined with vit D deficiency lead to an increased risk of hip fractures, making this animal model a possible tool for investigating measures to prevent such fractures.

Bone mass changes in weight-loaded and unloaded skeletal regions following a fracture of the hip.

Higher bone mineral density (BMD) has been reported in weight-loaded skeletal regions and lower BMD in unloaded regions in active athletes compared with controls. These discrepancies remain the first decades after cessation of active careers in former athletes with no remaining discrepancies found after age 65 years compared with age- and gender-matched controls. Physical activity is reduced after a hip fracture and BMD decreases in weight-loaded skeletal regions following the injury. If BMD increases in unloaded regions following a fracture of the hip it is not known. A BMD increase in an unloaded region would support the hypothesis of discrepancies in BMD response to physical activity in loaded and unloaded skeletal regions. BMD (g/cm2) was measured longitudinally using dual X-ray absorptiometry (DXA) in 32 women, mean age 77 years (range 57-90) and 12 men, mean age 74 years (range 53-89) with a hip fracture, the upper part of the skull representing an unloaded skeletal region, the arms a partly loaded region, and the femoral neck a weight-loaded region. Measurements (mean) were done in 11 days, 5 months, and 13 months after the hip fracture. Data are presented as mean +/- SEM. BMD increased in the upper part of the skull by 1.9%+/-0.8% the first 5 months and 3.7%+/-0.9% the first 13 months after the fracture (P < 0.05 and P < 0.001, respectively). BMD did not change in the arms but decreased in the nonfractured femoral neck by 4.7%+/-1.8% the first 5 months and 4.5%+/-1.7% the first 13 months after the fracture (both P < 0.01, respectively). In summary, in this longitudinal study, BMD increased in an unloaded skeletal region and decreased in a weight-loaded region following a hip fracture with reduced activity level, suggesting that loaded and unloaded skeletal regions confer different BMD response after changed activity level.

The impact of long-term moderate physical activity on functional performance, bone mineral density and fracture incidence in elderly women.

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.

Age, gender, and fragility fractures are associated with differences in quantitative ultrasound independent of bone mineral density.

Bone strength is determined by bone mineral density (BMD) and bone structure. Dual-energy X-ray absorptiometry (DXA) measures BMD. Whether quantitative ultrasound (qUS) measures a property of bone distinct from BMD is uncertain. To evaluate this, DXA and qUS were measured in 58 fracture patients and 428 controls. To study the independent effects of age and gender on qUS measurements and control for BMD by study design rather than statistical methods, subgroups from the normative database were created and intentionally matched by the same femoral neck (FN) BMD. Speed of sound (SOS; m/sec), broadband ultrasound attenuation (BUA; dB/MHz), and stiffness index (SI) were then compared in individuals matched by FN BMD but differing in age, gender, and presence or absence of fractures. The results are presented as percentage difference (mean +/- SD). Elderly women with the same FN BMD as young women had 1 +/- 2% lower SOS (p < 0.05), 8 +/- 15% lower SI (p < 0.05), and 4 +/- 9% lower BUA (p = 0.07). Elderly women with the same FN BMD as elderly men had 5 +/- 9% lower BUA (p < 0.05). Elderly men with the same FN BMD as young men had 1 +/- 2% lower SOS (p = 0.1), 5 +/- 14% lower SI (p = 0.2), and 1 +/- 9% lower BUA (n.s.). Young women with the same FN BMD as young men had 2 +/- 7% lower BUA (n.s.). Women with fragility fractures had 8 +/- 11% lower BUA (p < 0.001) and 13 +/- 22% lower SI (p < 0.01) than controls with no fractures matched by FN BMD, age, and gender. Men with fragility fractures had 13 +/- 12% lower BUA (p < 0.01) and 16 +/- 19% lower SI (p < 0.05) than controls with no fractures matched by FN BMD, age, and gender. Despite comparable femoral neck BMD, qUS measurements differed according to age, gender, and fracture status, suggesting that qUS may provide additional information independent of femoral neck BMD, such as differences in connectivity or other properties yet to be identified.

Exercise may induce reversible low bone mass in unloaded and high bone mass in weight-loaded skeletal regions.

Exercise during growth and adolescence increases bone mineral density (BMD) in weight-loaded skeletal regions. The development of BMD in unloaded or minimally loaded regions during activity is unclear. We measured BMD in one unloaded, one partly loaded and one highly loaded skeletal region in 67 active soccer players, mean age 22.7 years (range 17-35 years), 128 former soccer players, mean age 54.0 years (range 19-85 years) and 138 controls, mean age 50.6 years (range 19-80 years). The active soccer players played at three different levels: premier league, 3rd league or 6th league. Duration of exercise in these three grou s was 12, 8 and 6 h/week, respectively. BMD (g/cm ) was measured by dual-energy X-ray absorptiometry (DXA) in the upper part of the skull (the unloaded skeletal region), the arms (the partly loaded region) and the femoral neck (the maximal loaded region). Data are presented as mean +/- SD. Active soccer players had 10.3 +/- 10.4% lower BMD in the upper part of the skull (p < 0.001), 1.4 +/- 6.3% higher BMD in the arm (NS) and 12.7 +/- 9.8% higher BMD in the femoral neck (p<0.001) compared with age- and gender-matched controls. All three levels of soccer players demonstrated, independent of activity level, the same discrepancies in BMD compared with controls. Former soccer players had lower BMD in the upper part of the skull until age 70 years and higher BMD in the femoral neck until age 50 years compared with controls. The BMD of the arm was not different in former soccer players compared with controls. In summary, active soccer players had lower BMD in the unloaded skeletal region, no difference in BMD in the partly loaded region and higher BMD in the weight-loaded region compared with controls. The discrepancies compared with controls diminished with age so that no differences were found in BMD after age 70 years. In conclusion, unloaded and weight-loaded skeletal regions may respond differently to increased and decreased physical activity.

Bone loss following tibial osteotomy: a model for evaluating post-traumatic osteopenia.

The reduced bone mineral density (BMD) found in patients with fractures may, in part, follow rather than precede the fracture. We studied the magnitude and reversibility of bone loss in the 15 months following osteotomy in 21 men and 5 women with localized medial arthritis of the knee. BMD (mean +/- SD), measured using dual-energy X-ray absorptiometry, decreased by a maximum of 35 +/- 21% in the mid-diaphysis of the affected tibia at 9 months after surgery (p < 0.001). At 15 months, reversal of bone loss in non-fractured bones was incomplete; the remaining deficit was 20 +/- 27% relative to baseline (p < 0.001). Maximum bone loss occurred at 9 months at the total body (5 +/- 2%), spine (15 +/- 17%) and at Ward's triangle of the proximal femur of the unoperated limb (10 +/- 17%) (all p < 0.01). In summary, post-traumatic bone loss is region-specific with incomplete reversibility, at least after about 15 months. Deficits in BMD in cross-sectional studies of patients with fractures, held to be responsible for the bone fragility, may, in part, follow rather than precede the fracture.

Development and evaluation of three immunofluorometric assays that measure different forms of osteocalcin in serum.

BACKGROUND: Circulating human osteocalcin (hOC) has been used as a marker of bone formation. Our aim was to validate three immunofluorometric assays (IFMAs), measuring different forms of hOC. METHODS: The two-site IFMAs were based on previously characterized monoclonal antibodies. Assay 2 recognized intact hOC, assays 4 and 9 measured the NH(2)-terminal mid-fragment and the intact hOC. In addition, assay 9 required hOC to be gamma-carboxylated. RESULTS: A 76-79% increase of serum immunoreactive hOC was found in the postmenopausal group compared with the premenopausal group with all IFMAs. With EDTA-plasma samples, the observed increases were lower (49-65%). The hOC concentration in the postmenopausal group receiving hormone replacement therapy was 42-44% lower than that in the postmenopausal control group in both serum and EDTA-plasma samples. The depressed carboxylation in warfarin-treated patients was accompanied by lower results in assay 9. The ratio of assay 9 to assay 4 totally discriminated the warfarin-treated patients from the controls. Assay 9 showed the smallest decreases in measured hOC after storage of serum or plasma for 4 weeks at 4 degrees C, followed by assay 4 and assay 2. Results from the last assay were <17% of their initial values after 4 weeks of storage. No diurnal variation was observed with assay 9 as opposed to the two other IFMAs. CONCLUSION: The three assays with their distinct specificity profiles (intact vs fragmented and carboxylated vs decarboxylated hOC) may provide valuable tools for investigating the significance of different hOC forms in various bone-related diseases.

Changes in bone mineral, lean body mass and fat content as measured by dual energy X-ray absorptiometry: a longitudinal study.

Bone mineral density (BMD) and soft tissue composition were measured by dual energy X-ray absorptiometry (DXA) 3-4 years apart in 273 men and women aged 23-90. We found different rates of BMD loss in different skeletal regions. There were also different rates of BMD loss in different regions within the hip. Average rates of loss for male subjects 50 years of age and above for BMD total body were 0.1%/year and for femoral neck 1.5%/year, whereas lumbar spine (L2-L4) increased by 0.4%/year. Average rates of loss for female subjects 50 years of age and above for BMD total body were 0.0%/year, femoral neck 0.9%/year, and lumbar spine (L2-L4) 0.1%/year.