Loss of Bone Mineral Density in Women Athletes During Aging

Total and regional bone mineral density (BMD) by dual-energy-X-ray absorptiometry (DXA) and bone turnover were tested in 50 highly trained women athletes and 21 sedentary control women (18–69 years; BMI < 25 kg/m²). VO_2max (ml · kg⁻¹· min⁻¹) and lean tissue mass (DXA) were significantly higher in the athletes versus controls (both P < 0.0001). Total body BMD did not decline significantly with age in the athletes whereas lumbar spine (L₂–L₄) BMD approached statistical significance (r =−0.26; P= 0.07). Significant losses of the femoral neck (r =− 0.42), Ward's triangle (r =−0.53), and greater trochanter BMD (r =−0.33; all P < 0.05) occurred with age in the athletes. In the athletes, total body BMD, L₂–L₄ BMD, and BMD of all sites of the femur were associated with lean tissue mass (r = 0.32 to r = 0.57, all P < 0.05) and VO_2max (r = 0.29 to r = 0.48, all P < 0.05). Femoral neck and greater trochanter BMD were higher in the athletes than in controls (both P < 0.05) and lumbar spine and Ward's triangle BMD approached statistical significance (both P= 0.07). Bone turnover was assessed by serum bone-specific alkaline phosphatase (B-ALP), urinary deoxypyridinoline cross-links (Dpd), and urinary aminoterminal cross-linked telopeptides (NTX). There were no relationships between B-ALP or Dpd with age whereas NTX increased with age (r = 0.46, P < 0.05) in the entire group. Levels of B-ALP and NTX were negatively associated with total body, L₂–L₄, femoral neck, Ward's triangle, and greater trochanter BMD (P < 0.05). B-ALP and Dpd were not significantly different between athletes and controls whereas NTX was lower in the athletes than in controls (P < 0.001). The high levels of physical activity observed in women athletes increase aerobic capacity and improve muscle mass but are not sufficient to prevent the loss of bone with aging. Received: 28 November 1997 / Accepted: 8 April 1998     

Symmetry of Bone Mineral Density at the Proximal Femur with Emphasis on the Effect of Side Dominance

The symmetry and effect of side dominance on the bone mineral density (BMD) of proximal femur was evaluated in 266 normal Chinese women with a dual photon absorptiometer (DPA, Norland 2600). The BMDs of the femoral neck, trochanter, and Ward's triangle at the proximal femur in the dominant leg (BMDd) were compared with those of the nondominant side (BMDn). The linear regression of BMDd and BMDn of the corresponding regions at the proximal femur showed a good correlation (r = 0.893–0.941, SEE = 0.052–0.062 g/cm²). The paired difference of proximal femoral BMD was −0.002 ± 0.062 g/cm² for the femoral neck, 0.003 ± 0.054 g/cm² for the trochanter, and 0.008 ± 0.062 g/cm² for the Ward's triangle. The ratio of asymmetry for femoral neck BMD was mean ± SD =−0.4 ± 7.8%, for trochanter 0.6 ± 8.1%, and for the Ward's triangle 1.3 ± 9.7%. Both paired difference and ratio of asymmetry between BMDd and BMDn were approximately normally distributed, with a mean ± 2 SD ranging from −0.126 to 0.122 g/cm² for paired difference and −16.0% to 15.2% for the ratio of asymmetry in the femoral neck. These data revealed that dominance had little effect on the proximal femur BMDs. However, the wide range of paired difference and ratio of asymmetry of the proximal femur BMD in the normal individuals should be considered in the interpretation of the proximal femoral BMD. Received: 26 July 1996 / Accepted: 23 April 1997     

Correlation of Serum Osteocalcin Fractions with Bone Mineral Density in Women During the First 10 Years after Menopause

Serum immunoreactive osteocalcin (irOC) consists of two fractions that differ from each other by their affinity for hydroxyapatite. The high and low affinity fractions are referred to as irOC_bound and irOC_free, respectively. To evaluate whether these fractions are determinants for different characteristics of bone or bone metabolism, we have performed a cross-sectional study among 212 apparently healthy women between 20 and 90 years of age. Bone mineral density (BMD) was determined at the lumbar spine, and the right femur neck, trochanter, and Ward's triangle using dual-energy X-ray absorptiometry (DXA). Biochemical markers for bone formation and resorption were determined in serum and in urine. After classification according to menopausal age, an inverse correlation was found in the 1–10 years postmenopausal women between irOC_free and BMD, notably of the Ward's triangle and femur neck. It is concluded that in 1–10 years postmenopausal women, irOC_free is an independent marker for BMD, but that in other age groups the association is less clear or is absent. Received: 14 November 1997 / Accepted: 23 March 1998     

Bone Mass in Female Volleyball Players: A Comparison of Total and Regional Bone Mass in Female Volleyball Players and Nonactive Females

The purpose of this cross-sectional study was to evaluate bone mass in female athletes participating in an impact loading sport (volleyball), and especially to investigate whether any changes in bone mass might be related to the type and magnitude of weightbearing loading and muscle strength. The volleyball group consisted of 13 first division players (age 20.9 ± 3.7 years) training for about 8 hours/week, and the reference group consisted of 13 nonactive females (age 25.0 ± 2.4 years) not participating in any kind of regular or organized sport activity. The groups were matched according to weight and height. Areal bone mineral density (BMD) was measured in total body, head, lumbar spine, femoral neck, Ward's triangle, trochanter, the whole femur, and humerus using dual-energy-X-ray absorptiometry. Isokinetic concentric peak torque of the quadricep and hamstring muscles was measured using an isokinetic dynamometer. Compared with the controls, the volleyball players had a significantly (P < 0.05–0.01) higher BMD of the total body (6.1%), lumbar spine (13.2%), femoral neck (15.8%), Ward's triangle (17.9%), trochanter (18.8%), nondominant femur (8.2%), and humerus (dominant 9.5%, nondominant 10.0%), but not of the head and the dominant whole femur. The dominant humerus showed significantly higher BMD than the nondominant humerus in both the volleyball and nonactive group (P < 0.05). There was no significant difference in muscle strength of the thigh between the two groups. In the nonactive group, muscle strength in the quadriceps, and especially hamstrings, was correlated to BMD of the adjacent bones (whole femur, hip sites) and also to distant sites (humerus). However, in the volleyball group there were no correlations between muscle strength and BMD of the adjacent bones, but quadricep strength correlated to BMD of the humerus. These results clearly show that young female volleyball players have a high bone mass. The demonstrated high bone mass seems to be related to the type of loading subjected to each BMD site. Muscle strength of the thigh seems to have little impact on BMD in female volleyball players. Received: 18 June 1996 / Accepted: 31 October 1996     

How Hip and Whole-Body Bone Mineral Density Predict Hip Fracture in Elderly Women: The EPIDOS Prospective Study

We conducted a population-based cohort study in 7598 white healthy women, aged 75 years and over, recruited from the voting lists. We measured at baseline bone mineral density (BMD g/cm²) of the proximal femur (neck, trochanter and Ward's triangle) and the whole body, as well as fat and lean body mass, by dual-energy X-ray absorptiometry (DXA). One hundred and fifty-four women underwent a hip fracture during an average 2 years follow-up. Each standard deviation decrease in BMD increased the risk of hip fracture adjusted for age, weight and centre by 1.9 (95% CL 1.5, 2.3) for the femoral neck, 2.6 times (2.0, 3.3) for the trochanter, 1.8 times (1.4, 2.2) for Ward's triangle, 1.6 times (1.2, 2.0) for the whole body, and 1.3 times (1.0, 1.5) for the fat mass. The areas under the receiver operating characteristic (ROC) curves were not significantly different between trochanter and femoral neck BMD, whereas ROC curves of femoral neck and trochanter BMD were significantly better than those for Ward's triangle and whole-body BMD. emsp;Women who sustained an intertrochanteric fracture were older (84 ± 4.5 years) than women who had a cervical fracture (81 ± 4.5 years) and trochanter BMD seemed to be a stronger predictor of intertrochanteric ([RR = 4.5 (3.1, 6.5)] than cervical fractures ([RR = 1.8 (1.5, 2.3]). emsp;In very elderly women aged 80 years and more, hip BMD was still a significant predictor of hip fracture but the relative risk was significantly lower than in women younger than 80 years. emsp;In the 48% of women who had a femoral neck BMD T-score less than –2.5, the relative risk of hip fracture was increased by 3, and the unadjusted incidence of hip fracture was 16.4 per 1000 woman-years compared with 1.1 in the population with a femoral neck BMD T-score 5–1. Received: 19 May 1997 / Accepted: 16 October 1997     

Bone Mineral Density in the Chronic Patellofemoral Pain Syndrome

Bone mineral density (BMD) and clinical status of 40 patients with a chronic, unilateral patellofemoral pain syndrome (PFPS) were determinated. The mean duration of the disease at the time of the follow-up was 7.6 ± 1.8 (SD) years. The BMD was measured at the spine (L2–L4), and the femoral neck, trochanter area of the femur, distal femur, patella, proximal tibia, and calcaneus of both lower extremities using a dual-energy X-ray absorptiometric (DXA) scanner. The mean BMD of the affected limb (compared with the unaffected side) was significantly lower in the distal femur (−3.3%; P= 0.002), patella (−2.5%; P= 0.016), and proximal tibia (−1.9%; P= 0.008). The femoral neck, trochanter area of the femur, and calcaneus showed no significant side-to-side differences, and the spinal BMDs of men and women with the PFPS were comparable with the manufacturer's age-adjusted reference values for Western European men and women. The relative BMDs of the affected knee showed strongest correlation with the muscle strength of the same knee: the better the muscle strength compared with the healthy knee, the higher the relative BMD (r = 0.56–0.58 with P < 0.001 in each anatomic site of the knee). In the stepwise regression analysis, low body weight or low body mass index, high level of physical activity, the patient's good subjective overall assessment of his/her affected knee, and short duration of the symptoms were also independent predictors of the high relative BMD in the affected knee so that along with the muscle strength these variables could account for 51% of the variation seen in the relative BMD of the femur, 61% in the patella, and 54% in the proximal tibia. In conclusion, chronic patellofemoral pain syndrome results in a significantly decreased BMD in the knee region of the affected limb. The spine, proximal femur, and calcaneus are not affected. Recovery of normal muscle strength and knee function seems to be of great importance for good BMD. Received: 30 May 1997 / Accepted: 8 January 1998     

Bone Mass and Muscle Strength in Young Female Soccer Players

In this cross-sectional study, bone mass and muscle strength of the thigh were investigated in 51 female soccer players, age 16.3 ± 0.3 years, who had been playing soccer for 8.1 ± 2.1 years and were at the time of the study in soccer training for 5.0 ± 1.7 hours/week. They were compared with 41 nonactive females, age 16.2 ± 1.3 years. The groups were matched according to age, weight, and height. Areal bone mineral density (BMD) was measured of the total body, head, lumbar spine, femoral neck, Ward's triangle, and the greater trochanter using dual energy X-ray absorptiometry (DXA). Isokinetic muscle strength of the quadriceps and hamstrings muscles was measured using an isokinetic dynamometer. Compared with the nonactives, the soccer players had significantly higher BMD of the total body (2.7%), lumbar spine (6.1%), the dominant and nondominant hip (all sites). The largest differences were found in the greater trochanter on both sides (dominant, 16.5%, nondominant, 14.8%). The soccer players had significantly higher concentric and eccentric peak torque of the thigh muscles. In the soccer group, there was only a positive association between thigh muscle strength and BMD of the adjacent hip, and in the nonactive group there were several positive associations between muscle strength and BMD. However, when adjusting for the variation in weight and height all these associations became nonsignificant. Using multiple linear regression, the type of activity (soccer player, nonactive) independently predicted BMD of all dominant hip sites (β= 0.32–0.48, P < 0.01). No other variable was found to independently predict BMD of any site. In the younger subjects (≤16 years) only BMD of the greater trochanter was significantly higher in the soccer players. In the older subjects (>16 years) the soccer players had significantly higher BMD in all measured sites except for the nonweight-bearing head. The differences in muscle strength between soccer players and nonactives were already seen in the young age group. In conclusion, girls who train and play soccer in adolescence have a higher bone mass in the hip and lumbar spine, and a higher muscle strength of the thigh compared with nonactive controls, indicating a site-specific skeletal response of weight-bearing and impact-loadng acting on the skeleton. The differences in bone mass were already apparent in early adolescence, but became more pronounced in late adolescence, probably explained by a longer exposure to soccer training with time. Our results also indicate that muscle strength in itself might not be of decisive importance for bone mass in the hip of adolescent females. Received: 18 December 1998 / Accepted: 14 April 2000     

Dissimilar Spine and Femoral Z-Scores in Premenopausal Women

The purpose of this study was to determine if differences exist in premenopausal women between z-scores for lumbar spine and proximal femoral bone mineral densities (BMD). Participants were 237 women ranging in age from 20 to 45 years. BMDs of the lumbar spine and proximal femur (femoral neck, Ward's area, and trochanter) were assessed using dual-energy X-ray absorptiometry (Lunar DPX). Mean (±SD) age, height, and weight of the participants were 29.4 ± 6.9 years, 164.4 ± 6.1 cm, and 64.9 ± 12.1 kg, respectively. Lumbar spine BMD and BMD at the femoral neck, Ward's area, and trochanter were significantly correlated with large SEEs (r = 0.59–0.65; SEE = 0.09–0.11). No positive correlation with age and BMD at any site was seen in this population but a significant negative correlation with age was seen in the proximal femur beginning at age 30. Twenty to 24% of the 20–29-year-olds exhibited a difference in z-scores of greater than 1 between the spine and sites in the proximal femur. This percentage increased to 32–46% in the 30–45-year-olds but the nature of the observed differences changed. The differences in spine and proximal femoral z-scores that are seen in the older age group appear to be the result of the earlier onset of bone loss in the proximal femur rather than an initial difference in peak bone mass which has been maintained. Received: 28 August 1996 / Accepted: 25 April 1997     

Circulating β2 Microglobulin in Relation to Bone Metabolism: Implications for Bone Loss with Aging

The aim of this cross-sectional study was to evaluate the relationships between circulating β₂ microglobulin (β₂ m) and bone mineral density (BMD), parameters of bone remodeling, vitamin D metabolites, parathyroid hormone (PTH), estradiol levels, and age in a group of 165 clinically healthy or osteoporotic, but otherwise normal untreated women. In this group of women, systemic β₂ m correlated with BMD (g/cm²) levels for total hip and Ward's triangle (r =−0.298, P < 0.0001; and r =−0.299, P < 0.0001, respectively), but only at the borderline level with BMD at the spine (r =−0.145, P= 0.0604). Serum β₂ microglobulin markedly correlated with age (r = 0.512, P= 0.0001). β₂ m levels correlated with indices of bone remodeling, as well as with serum creatinine and estradiol levels. However, after stratification of all analyses by age, body mass index, and serum 25OHD₃, 1,25(OH)₂D₃, PTH, or estradiol levels (using standard multiple regression and stepwise forward regression models), only 25OHD₃ was found to be an independent predictor of BMD at the hip, including Ward's triangle, as estradiol of BMD at the spine. On the other hand, β₂ m was not associated with BMD at any of the measured regions. Also, no association was found between serum PTH and BMD values. Therefore, systemic β₂ m seems to be an indicator of bone remodeling in the course of natural skeletal aging rather than a variable independently predicting bone loss. Received: 21 July 1998 / Accepted: 10 June 1999     

Bone Mineral Content and Density in Professional Tennis Players

Total and regional bone mineral content (BMC) as well as lean and fat mass were measured in nine male professional tennis players (TPs) and 17 nonactive subjects; dual-energy X-ray absorptiometry (DXA) was used for measuring. The mean (±SD) age, body mass, and height were 26 ± 6 and 24 ± 3 years, 77 ± 10 and 74 ± 9 kg, and 180 ± 6 and 178 ± 6 cm for the TP and the control group (CG), respectively. The whole body composition for BMC, lean mass, and fat of the TP was similar to that observed in the CG. The tissue composition of the arms and legs was determined from the regional analysis of the whole-body DXA scan. The arm region included the hand, forearm, and arm, and was separated from the trunk by an inclined line crossing the scapulo-humeral joint. In the TP, the arm tissue mass (BMC + fat + lean mass) was about 20% greater in the dominant compared with the contralateral arm because of a greater lean (3772 ± 500 versus 3148 ± 380 g, P < 0.001) and BMC (229.0 ± 43.5 versus 188.2 ± 31.9 g, P < 0.001). In contrast, no significant differences were observed either in BMC or BMD between arms in the CG. Total mass, lean mass, and BMC were greater in the dominant arm of the TP than in the CG (all P < 0.05). In the TP, BMD was similar in both legs whereas in the CG, BMD was greater in the right leg. Lumbar spine (L2–L4) BMD, adjusted for body mass and height, was 15% greater in the TP than in the CG (P < 0.05). Femoral neck BMDs (femoral neck, Ward's triangle, greater trochanter, and intertrochanteric regions) adjusted for body mass and height were 10–15% greater in the TP (all P < 0.05). Ward's triangle BMD was correlated with the maximal leg extension isometric strength (r = 0.77, P < 0.05) even when adjusted for body mass (r = 0.76, P < 0.05) and height (r = 0.77, P < 0.05). In summary, the participation in tennis is associated with increased BMD in the lumbar spine and femoral neck. These results may have implications for devising exercise strategies in young and middle-aged persons to prevent involutional osteoporosis later in life. Received: 29 April 1997 / Accepted: 14 November 1997     

High Intensity Resistance Training: Effects on Bone in Older Men and Women

There is evidence that high intensity resistance training promotes bone maintenance in older women, however, the effect of high intensity free weight training has not been investigated in older men or women. Furthermore, little is known about the chronic effect of weight training on serum insulin growth factor-I (IGF-I) in this population. We compared the effects of a moderate intensity seated resistance-training program with a high intensity standing free weight exercise program on bone mass and serum levels of IGF-I and IGFBP3 in healthy older men and women. Twenty-eight men (54.6 ± 3.2 years) and 26 nonestrogen-replaced women (52.8 ± 3.3 years) served as their own controls for 12 weeks, then were randomly assigned to a moderate or high intensity training group and trained three times/week for 24 weeks. Prior to and after the control period and at the end of training, bone mass and body composition were assessed by dual energy X-ray absorptiometry (DXA), muscle strength by isokinetic dynamometry, muscular power by Wingate Anaerobic Power Test, and IGF-I by radioimmunoassay (RIA). A repeated measures analysis of covariance (ANCOVA) revealed that high intensity training resulted in a gain in spine BMD in men (1.9%), P < 0.05, but not in women, whereas moderate intensity training produced no changes in either gender at this site. Increases were observed at the greater trochanter, P < 0.03, in men regardless of training intensity, but not in women at any hip site. However, when compared with zero, both men and women in the high intensity group demonstrated significant increases in trochanteric BMD (1.3% and 2.0%, respectively) and a decrease in femoral BMD (−1.8%). Neither circulating serum IGF-I nor IGFBP3 were altered by either training regimen, but both training programs resulted in improvements in total body strength (37.62%) and lean mass (males 4.1%, females 3.1%). We conclude that although resistance training of moderate to high intensity produced similar muscle changes in older adults, a higher magnitude is necessary to stimulate osteogenesis at the spine. However, at the spine, intensity was not sufficient to offset low levels of estrogen in early postmenopausal women. Furthermore, bone changes were not accompanied by changes in circulating serum levels of IGF-I or IGFBP3. Received: 21 July 1999 / Accepted: 11 January 2000     

Lateral Spine Densitometry in Obese Women

The lateral (LAT) spine scan has been suggested as a more sensitive measure than posterior-anterior (PA) scanning for assessing age-related bone loss in normal-weight postmenopausal women. The measurement error of PA and LAT bone mineral density (BMD) using dual energy X-ray absorptiometry (DXA) has also been shown to rise with incremental increases in fat and from large variance in fat thickness, respectively. The purpose of this cross-sectional study was to determine specific affects of obesity on paired PA and LAT lumbar (L₂–L₄) BMD and Z score (BMD of patient versus age-matched reference database) correlation in 30 obese postmenopausal women (mean BMI ± SD = 33.3 ± 4.06). The mean PA and LAT BMD ± SD were 0.946 ± 0.123 and 0.749 ± 0.134, respectively. The mean PA and LAT Z scores were −0.17 ± 1.15 and 0.80 ± 1.7. The correlation between PA and LAT BMD was significantly lower (r = 0.55; P < 0.05) than previously reported, and PA and LAT Z score correlation was (r = 0.57; P= 0.0016). After adjusting for body mass index (BMI), percent body fat, fat mass, and truncal fat by DXA, waist:hip ratio (WHR) and visceral and subcutaneous abdominal fat by computerized axial tomography (CT), PA and LAT Z score correlation increased to r = 0.62; P= 0.0065. In our subjects, the mean LAT Z score was 4.6 times higher than the mean AP Z, contrary to previous observations in normal-weight postmenopausal women. Our findings may be due to increased soft tissue composition and fat inhomogeneity in the LAT scanning field resulting in increased X-ray attenuation in obesity. Received: 22 July 1997 / Accepted: 26 January 1998     

Bone density of the radius,spine, and hip in relation to percent of ideal body weight in postmenopausal women

Summary Bone mineral content (BMC) and bone mineral density (BMD) of the spine (L2–L4) and hip (at femoral neck, Ward's triangle, and greater trochanter sites) were determined by dual-photon absorptiometry (DPA), and of the radius by single-photon absorptiometry (SPA) in healthy postmenopausal women aged 40–70 years. The relationships of BMC and BMD to years since menopause were examined separately in 97 women who were above 115% of ideal body weight (IBW) and in 128 women below. The heavier women had significantly greater mean BMC and BMD at each site than did the normal-weight women. In the normal-weight women, there was a significant negative correlation between BMD and years since menopause at each measurement site except the greater trochanter. In the obese women, BMD decreased with increasing years since menopause at the radius site only and BMC declined with increasing years after menopause at the hip (femoral neck and Ward's triangle region) as well as the radius. Thus, body size is a significant determinant of BMD in this population. The pattern of loss of BMD from Ward's triangle and femoral neck regions of hip are similar to that of the spine. The BMC and BMD findings in the hip suggest that remodeling occurs at this weight-bearing site which has a favorable effect on bone strength.     

Effects of Risedronate Treatment on Bone Density and Vertebral Fracture in Patients on Corticosteroid Therapy

Men and women (n = 518) receiving moderate-to-high doses of corticosteroids were enrolled in two studies with similar protocols and randomly assigned to receive either placebo or risedronate (2.5 or 5 mg) for 1 year. All patients received daily calcium supplementation (500–1000 mg), and most also received supplemental vitamin D (400 IU). The primary endpoint was the difference between the placebo and active groups in lumbar spine bone mineral density (BMD) at 1 year; changes in BMD at other sites, biochemical markers of bone turnover, and the incidence of vertebral fractures were also assessed. In the overall population, the mean (SE) lumbar spine BMD increased 1.9 ± 0.38% from baseline in the risedronate 5 mg group (P < 0.001) and decreased 1.0 ± 0.4% in the placebo group (P= 0.005). BMD at the femoral neck, trochanter, and distal radius increased or was maintained with risedronate 5 mg treatment, but decreased in the placebo group. Midshaft radius BMD did not change significantly in either treatment group. The difference in BMD between the risedronate 5 mg and placebo groups was significant at all skeletal sites (P < 0.05) except the midshaft radius at 1 year. The 2.5 mg dose also had a positive effect on BMD, although of a lesser magnitude than that seen with risedronate 5 mg. A significant reduction of 70% in vertebral fracture risk was observed in the risedronate 5 mg group compared with the placebo group (P= 0.01). Risedronate was efficacious in both men and women, irrespective of underlying disease and duration of corticosteroid therapy, and had a favorable safety profile, with a similar incidence of upper gastrointestinal adverse events in the placebo and active treatment groups. Daily treatment with risedronate 5 mg significantly increases BMD and decreases vertebral fracture risk in patients receiving moderate-to-high doses of corticosteroid therapy. Received: 11 October 1999 / Accepted: 1 May 2000 / Online publication: 27 July 2000     

Body Size Accounts for Most Differences in Bone Density Between Asian and Caucasian Women

We compared bone mineral density (BMD) of the whole body (and subregions: arm, leg, and pelvis), hip, spine, lateral spine, wrist, and forearm among Caucasian and Asian women at four geographic centers (Honolulu, HI; Nottingham, UK; Portland, OR; Copenhagen, Denmark). Data were derived from the baseline examination of 1367 Caucasian and 162 Asian women enrolled in the 1609-subject Early Postmenopausal Interventional Cohort (EPIC) study. After adjusting for age, study site, years postmenopause, and years of estrogen use, BMD was approximately 4–6% lower (P < 0.05) among Asian women at most skeletal sites, but there was no significant difference for wrist or forearm BMD. Adding height, lean body mass, fat mass, and/or quadriceps muscle strength to the regression models reduced the racial differences at most skeletal sites; after these additional adjustments, Asian women had significantly lower BMD only for the lateral spine (−4.4%; P < 0.005), arm (−2.20%; P < 0.05) and leg (−1.65%; P < 0.05), whereas the wrist was significantly greater (4.64%; P < 0.005) for Asian women. Further research is needed to determine why racial differences in BMD persist at certain skeletal sites, but not others, after adjusting for body size. Received: 22 January 1996 / Accepted: 3 May 1996     

Bone Mineral Density and Bone Turnover in Patients with Knee Osteoarthritis Compared with Generalized Osteoarthritis

The aim of this study was to investigate bone mineral density (BMD) and bone turnover in patients with primary knee osteoarthritis (KOA) and to compare them with generalized OA (GOA) and nonGOA patients. A total of 88 postmenopausal primary KOA patients were studied. OA was graded by using knee radiographs. BMD of the lumber spine, femur, and radius, and biochemical markers of bone turnover, pyridinoline (Pyr), deoxypyridinoline (Dpyr), CTx, and osteocalcin were compared among each grade. BMD was also compared with 88 normal controls who were age and weight-matched. In 88 KOA patients, 56 were divided into 28 GOA and 28 non-GOA groups by grading hand radiographs. BMD and biochemical markers were compared between GOA and non-GOA. KOA patients had higher BMD at several skeletal sites compared with age- and weight-matched normals. A significant difference of BMD between each grade was observed between grades 0–1 and 3 (0.774 ± 0.143 versus 0.940 ± 0.185 g/cm², P < 0.001), grades 2 and 3 (0.781 ± 0.125 versus 0.940 ± 0.185 g/cm², P < 0.01) in the spine, and between grades 0–1 and 3 (0.505 ± 0.100 versus 0.564 ± 0.127 g/cm², P < 0.05) in the trochanter. A significant difference of biochemical bone markers was observed between grades 0–1 and 3 (P < 0.05) and between grades 2 and 3 (P < 0.05) in Pyr and grades 0–1 and 3 (P < 0.05) and between grades 1 and 4 (P < 0.05) in Dpyr, but not in osteocalcin and CTx. GOA patients had higher BMD of the spine (0.902 ± 0.175 versus 0.747 ± 0.138 g/cm², P < 0.01), trochanter (0.535 ± 0.107 versus 0.480 ± 0.107 g/cm², P < 0.05), and one-third of the radius (0.526 ± 0.068 versus 0.472 ± 0.089 g/cm², P < 0.05) and had significantly higher biochemical markers in Pyr and Dpyr than non-GOA patients. It is concluded that KOA patients had higher BMD at several skeletal sites. Biochemical bone markers were influenced by some degree of cartilage damage in OA patients. This tendency was stronger in GOA patients than in non-GOA patients. Received: 12 February 1999 / Accepted: 2 November 1999     

High Bone Turnover is Associated with Low Bone Mass and Spinal Fracture in Postmenopausal Women

A group of 366 healthy, white postmenopausal women, aged 50–81 years, mean age 66 years, were selected from the screened population of Scandinavians who were part of a multicenter study of the efficacy of tiludronate, a new bisphosphonate, in established postmenopausal osteoporosis. Eighty-eight women had a lumbar spine bone mineral density (BMD) above 0.860 g/cm², and 278 women had a BMD below 0.860 g/cm². Spinal fracture was diagnosed from lateral spine X-ray studies and defined as at least 20% height reduction (wedge, compression, or endplate fracture) in at least one vertebra (T4–L4). Bone resorption was assessed by measurement of the urinary excretion of type I collagen degradation products by the CrossLaps™ enzyme-linked immunoassay (ELISA). Bone formation was assessed by ELISA measurement of the N-terminal-mid-fragment as well as the intact serum osteocalcin (OC_N-MID), thus omitting the influence of the instability of osteocalcin caused by the labile 6 amino acid C-terminal sequence. The women were divided into groups with high or low bone turnover according to the concentrations of urinary CrossLaps™ or OC_N-MID. Women in the quartiles with the highest concentrations of CrossLaps [519 ± 119 μg/mmol (SD)] or OC_N-MID [44.6 ± 7.5 ng/ml (SD)] had 10–16% lower spinal BMD compared with women in the lowest quartiles (CrossLaps 170 ± 48 μg/mmol (SD), and OC_N-MID [22.1 ± 3.0 ng/ml (SD)] (P < 0.0004). The prevalences of spinal fracture were 25 to 29% in the lowest quartiles, whereas the prevalences in the highest quartiles were almost double—53–54% (P < 0.006). If the women were subgrouped according to spinal BMD and prevalence of spinal fracture, corresponding results were found. Women with a BMD less than 0.860 g/cm², without or with spinal fracture (n = 136 and n = 142), had 36–43% higher concentration of CrossLaps (P= 0.0001) and 11–15% higher concentration of OC_N-MID (P < 0.02), as compared with women with a BMD above 0.860 g/cm² and no spinal fracture (n = 84). In conclusion, the results indicate a strong association among high bone turnover, low bone mass, and prevalence of spinal fracture, which supports the theory that high bone turnover is a risk factor for spinal fracture and osteoporosis. Received: 29 February 1996 / Accepted: 9 August 1996     

Bone Mineral Density of the Skull in Premenopausal Women

Dual-energy X-ray absorptiometry (DXA) of the head has received little attention. We used DXA to measure bone mineral density (BMD) of the entire skull including the mandible (BMD_Head) and BMD of the cranial vault (BMD_Vault) in 91 normal young women. We also measured BMD of the total body (BMD_{Total body}), proximal femur (``total femur'), and lumbar vertebrae (L1–L4). BMD (g/cm²; mean ± SE) was 1.032 ± 0.011 for L1–L4, 0.995 ± 0.011 for total femur, and 2.283 ± 0.028 for BMD_Vault (cranial vault) and the mean body weight of all subjects was 59.8 kg. Correlation between BMD_Vault and BMD_Head was 0.991 and this was not different from 1.0 (P= 0.473). The average difference between BMD_Vault and BMD_Head was −0.004 g/cm² suggesting that these two measurements of bone mass of the skull were similar. To determine the correlation between the different variables after accounting for external sources of variation, partial correlation derived from multiple regression was determined. Correlations between BMD at the various locations and with BMD_{Total body} were moderate to strong. Although small in magnitude, the partial correlations of body weight with BMD_{Total body}, total femur, and L1–L4 were significantly different from zero (P < 0.02). The results show that BMD_Vault, total femur, and L1–L4 were of equal value in predicting BMD_{Total body} and further, BMD_Vault was not influenced by body weight. Including body weight in multiple regression in addition to total femur or L1–L4 removed the extraneous variation due to body weight, and predictions of BMD_{Total body} were as reliable as when BMD_Vault was based on goodness of fit tests (P= 0.314). The technique used to measure BMD of the cranial vault is a relatively new variation of DXA technology. The precision was as good as other measurements of bone mass of the entire skull (including the mandible). Because the cranial vault is less sensitive to mechanical influences, it may be a region where response to therapy could be evaluated. The cranial vault may be a useful area to study certain heritable diseases that affect the skeleton, skeletal artifact, or evaluation of oral bone loss. Received: 22 December 1995 / Accepted: 24 September 1996     

Influence of Grip Strength on Metacarpal Bone Mineral Density in Postmenopausal Japanese Women: A Cross-Sectional Study

Most published studies on the role of muscle strength in the maintenance of bone mineral density (BMD) focused on the relationship between specific muscle groups and adjacent bones, mostly in young and premenopausal women. This study examined the influence of grip strength on BMD of the metacarpal index in postmenopausal Japanese women. Subjects included 1168 postmenopausal women aged 40–70 years. BMD measurement was done with computed X-ray densitometry (CXD) by analyzing X-ray films of the right second metacarpal index. Grip strength was measured in both the dominant and nondominant hands using a squeeze dynamometer. Grip strength (r = 0.2474; P= 0.0001) and age (r =−0.5443; P= 0.0001) significantly correlated positively and negatively, respectively, with BMD. Physical activity (r = 0.1318; P= 0.0001) also correlated positively with BMD. Breastfeeding (r =−0.1658; P= 0.0001), however, correlated negatively with BMD. Subjects with a history of regular physical activity had higher grip strengths and BMD, than those with no physical activity. Adjustment for age, physical activity, calcium intake, BMI, breastfeeding, testing site, and menopausal type indicated a significant (P for trend = 0.0013) positive association of grip strength with BMD. Subjects with stronger grip strengths had a decreased risk for low BMD. Received: 24 February 1998 / Accepted: 7 August 1998     

Absence of Linkage for Bone Mineral Density to Chromosome 12q12-14 in the Region of the Vitamin D Receptor Gene

Polymorphisms in the region of the gene for the vitamin D receptor (VDR) (chromosome 12q12-14) have been associated with differences in bone mineral density (BMD) in some studies but not in others. Because linkage analysis assesses allele sharing identical-by-descent among relatives instead of the association of a particular allele of an anonymous marker, we have performed a linkage study for bone BMD using microsatellite markers flanking the VDR locus. The present study explores whether or not relatives who share the chromosomal region containing the VDR gene have more similar bone density. Participants in the Framingham Osteoporosis Study (aged 37–89 years) who had undergone BMD testing were used to test for concordance of genotype with phenotype in the hip (femoral neck, Ward's area, trochanter) and lumbar spine (L2-L4) with adjustment for covariates. Multipoint quantitative trait linkage analysis using variance components methods was conducted with microsatellite markers flanking the VDR locus (GATA91H06, GATA5A09, GGAT2G06) in 332 extended families containing 1062 individuals with both bone density measures and marker data. In addition, quantitative trait sib-pair linkage analysis, with a marker (AFM345xf1) in close proximity to the VDR locus, was performed in a second sample of 169 sibships (n = 413), comprising 284 full-sib pairs. Neither analysis revealed evidence for linkage of this region to femoral neck, Ward's area, lumbar spine, and trochanter in age or sex BMI, and height-adjusted bone density measures. Additional adjustment for alcohol intake, caffeine consumption, smoking status, and estrogen supplement (female only) did not alter the results. The present study could not demonstrate linkage of BMD to chromosome 12q12-14. These findings suggest that neither the VDR gene nor other genes at this locus are likely to have a substantial impact upon bone density. Received: 23 February 2000 / Accepted: 3 August 2000 / Online publication: 22 December 2000