Influence of body weight on rates of change in bone density of the spine,hip, and radius in postmenopausal women

Summary Interrelationships between percent of ideal body weight (%IBW), serum estrogen levels, and change in bone mineral density (BMD) and bone mineral content (BMC) were studied in 288 postmenopausal women aged 41–71 years who participated in a 2-year calcium supplement trial. The spine (L2–L4) and femoral neck were measured by dualphoton absorptiometry, and the radius was measured by single-photon absorptiometry. Years since menopause, calcium intake, and initial BMD or BMC were included as independent variables in two-phase regressions of BMD and BMC on %IBW. Increased %IBW protected against loss of spine BMD [regression slope estimate=0.05, 95% C.I.: (0.03, 0.26)] and BMC in women up through about 106 %IBW but not in heavier women. Increased %IBW was not significantly related to BMD or BMC at the femoral neck or radius. Women above 106%IBW had significant gains in spine and femoral neck area (P< 0.05). Serum estrone and estradiol were positively correlated with BMD and BMC at the femoral neck only.     

Vitamin D receptor initiation codon polymorphism, bone density and inflammatory activity of patients with ankylosing spondylitis

Objectives Osteoporosis is a common finding in ankylosing spondylitis (AS) and may contribute to spinal deformity and bone pain. Bone metabolism as well as inflammatory processes are influenced by the vitamin D receptor gene (VDR). We investigated initiation codon (FokI) and 3UTR (BsmI) polymorphisms of the VDR for whether there could be an association with bone mineral density (BMD) in relation to bone metabolism or inflammatory activity in patients with AS.Methods In this study, 104 patients with AS (m/w 71/33, mean age 41±12 years) were investigated for their lumbar and femoral BMD by DEXA and in part by QCT measurements and compared to 54 healthy controls. Disease activity indices, serum markers of bone metabolism and inflammation were recorded. FokI and BsmI polymorphisms of the VDR were genotyped using genomic DNA from peripheral leukocytes with present or absent restriction sites defined as alleles f and b or F and B, respectively.Results In male AS patients, FokI genotypes were significantly associated with spinal but not with femoral BMD values (P=0.01) as independent predictors of low BMD, which was also influenced by BMI, and inflammatory and pain indices. CRP and ESR values were also significantly associated with FokI genotypes. BMD in female patients showed no significant association with either FokI or BsmI genotypes of the VDR.Conclusion This is the first evidence that the VDR gene may be involved in BMD differences, bone metabolism and inflammatory processes in ankylosing spondylitis. A possible interaction of the vitamin D system, cytokines and bone could define new diagnostic and therapeutic implications in ankylosing spondylitis.     

Pulsed estrogen therapy in prevention of postmenopausal osteoporosis. A 2-year randomized,double blind,placebo-controlled study

The aim of this study was to evaluate the efficacy of pulsed estrogen therapy (intranasal 17-estradiol) in the prevention of postmenopausal bone loss. A total of 386 women (40–65 years old), less than 5 years past menopause, were randomized to intranasal placebo, 17-estradiol 150 µg, or 300 µg daily for 2 years. Women with an intact uterus received micronised progesterone 200 mg per day, 14 days of each 28-day cycle. Women randomised to placebo-treatment received placebo progesterone. The primary endpoints were changes in BMD at the spine (L2–L4) and femoral neck. Secondary endpoints were changes in bone turnover markers: serum osteocalcin (sOC) as a marker of bone formation and urinary C-terminal telopeptides (uCTX) as a marker of bone resorption. BMD increased at all measured sites in women receiving active treatment in a dose-related manner, the difference compared to placebo being 5.2% and 6.7% at the spine, and 3.2% and 4.7 % at the hip, respectively, with 150 g and 300 g (P<0.001). On the other hand, a decrease versus baseline of –3.2% and –3.3% at the spine and hip, respectively, was observed in women receiving placebo (P<0.001). In the patients with at least one risk factor for osteoporotic fracture, the difference between placebo and 150 g or 300 µg was even higher at the spine (5.4% and 7.4%, respectively), and at the femoral neck (4.0% and 5.2%, respectively). Correspondingly, uCTX decreased from baseline by 39% and 46 %, and sOC by 22% and 27%, in the 150 µg group and 300 µg group (all P<0.001 versus placebo). A strong correlation was found between variations of bone turnover markers after 1 year and BMD after 2 years, emphasizing that bone markers can predict BMD response during hormonal treatment. Acceptability and general tolerance were good. This study demonstrates that pulsed estrogen therapy at the dose of 150 g and 300-g per day prevents bone loss in a dose-dependant manner at each site studied, and normalizes bone turnover markers to premenopausal levels.     

Regulation of mineral-to-matrix ratio of lumbar trabecular bone in ovariectomized rats treated with risedronate in combination with or without vitamin K<Subscript>2</Subscript>

The relationship between bone turnover and bone tissue and material properties was examined in ovariectomized (OVX) rats treated with risedronate in combination with or without vitamin K₂. Seventy female rats, 18 weeks of age, were assigned to 7 groups (n = 10): sham-operated + vehicle control; OVX + vehicle control; OVX + risedronate 0.1, 0.5, or 2.5mg/kg/day po; OVX + vitamin K₂ 30mg/kg/day po; OVX + vitamin K₂ (30mg/kg/day) and risedronate (0.5mg/kg/day). Treatments were given daily for 9 months. To assess bone turnover, we measured serum osteocalcin and urinary deoxypyridinoline at 0, 3, and 9 months. To assess vertebral and femoral tissue and material properties, bone mass, bone mineral density (BMD by DXA), trabecular bone structure (vertebra: 3D-CT), cortical bone structure (femur: histomorphometry), biomechanical properties, and mineral properties (mineral-to-matrix and carbonate-to-phosphate ratios by Fourier transform infrared microspectroscopy) were measured ex vivo at 9 months. Ovariectomy increased bone turnover and induced significant loss of bone mass/density, structure, mineral properties (mineral-to-matrix ratio), and strength. Risedronate produced dose-dependent inhibition of the ovariectomy-induced increase in turnover and loss of bone mass/density, structure, mineral-to-matrix ratio, and strength, with a lowest effective dose of 0.1–0.5mg/kg/day. High-dose risedronate (2.5mg/kg/day) did not induce increases in any parameter above that of sham control. Vitamin K₂ had no effects. In the OVX groups, urinary deoxypyridinoline at 3 and 9 months correlated significantly with vertebral BMD, trabecular bone volume, ultimate load, stiffness, and mineral-to-matrix ratio, and with femoral BMD, cortical area, and ultimate load. These results support the concept that changes in bone tissue and material properties can result directly from changes in bone turnover. Different effects among different drugs on material properties, including mineral-to-matrix ratio, may reflect differences in the relative rate and magnitude of osteoclastic bone resorption and osteoblastic primary bone mineralization.     

Effects of physical activity and dietary calcium intake on bone mineral density and osteoporosis risk in a rural Thai population

The objective of the study was to determine the effects of modifiable risk factors on bone mineral density in postmenopausal Thai women. Dietary calcium intake (g/day), energy expenditure (kcal/day), and sunlight exposure (h/day) were assessed in 129 rural Thai women aged 63 years (range 50 to 84 years). Bone mineral density (BMD) at the femoral neck, lumbar spine, and distal radius were measured by dual-energy X-ray absorptiometry (DXA). The average dietary calcium intake was 236 ± 188 g/day (mean ± SD), while the energy expenditure was 2,118 ± 656 kcal/day with 1.1 ± 1.7 h of sunlight exposure. In multiple linear regression analysis, dietary calcium intake, energy expenditure, and years since menopause were significant and independent predictors of BMD at various sites. The three factors together accounted for between 35% and 45% of the variance of BMD. The prevalence of osteoporosis (defined as BMD T-scores –2.5) was 33% at the femoral neck, 42% at the lumbar spine, and 35% at the distal radius. The risk of osteoporosis was higher in women with lower dietary calcium intake (138 mg/day; prevalence rate ratio [PRR], 1.4; 95% confidence interval [CI], 1.0 to 1.9), lower energy expenditure (1,682 kcal; PRR, 1.7; 95% CI, 1.2 to 2.3), and greater years since menopause (6 years; PRR, 2.6; 95% CI, 1.2 to 5.8). The population attributable risk fraction of osteoporosis risk due to the three factors was 70%. These results suggest that in the Thai population, low dietary calcium intake and low physical activity together with advancing years since menopause were independent risk factors for low BMD.     

Spine and femur densitometry at the menopause: Are both sites necessary in the assessment of the risk of osteoporosis?

Summary The aim of our study was to compare the results provided by the measurement of vertebral and femoral bone mineral density (BMD) for assessing the individual risk of osteoporosis as defined by either low BMD and/or rapid bone loss. Vertebral and femoral BMD were measured twice at a mean interval of 21 months in 85 normal, early post-menopausal women who had passed a natural menopause 6 months to 3 years previously. According to the measurement site, 36% (spine), 29% (femoral neck), 35% (Ward's triangle), and 25% (trochanter) fall in the at risk category, defined by a BMD value of 1 SD or more below the normal values for premenopausal women. Based on vertebral BMD, 39–48% of the women at risk had a normal femoral BMD. On the other hand, 24–37% of the women classified at risk based on femoral BMD maintained a low risk at the vertebral level. The annual rate of bone loss was significantly greater for the Ward's triangle (-2.7±3.8%) and femoral neck (-2.1±2.5%) than for the spine (-1.5±2.1%) and trochanter (-1.5±3.4%). There was a significant relationship between the rate of loss measured at the spine and femoral levels (r=0.34–0.58). Among the 21 women with a rapid vertebral bone loss, 48–67% had a low bone loss at the femoral level and vice versa. The ratio between mean rate of loss and the precision of the measurement sites was greater for the spine (1.6) compared with the femur (1.1–0.71). Our results indicate that vertebral and femoral BMD measurements produce discordant results in assessing the individual risk for osteoporosis.     

Effect of alendronate on bone mineral density and bone turnover in Thai postmenopausal osteoporosis

Alendronate has recently been approved for the prevention and treatment of postmenopausal osteoporosis, and its efficacy has been demonstrated in many Western countries. Our present study was performed to evaluate the effect of alendronate on bone mineral density (BMD) and its tolerability in Thais. Eighty postmenopausal women with osteoporosis participated in this study. After giving informed consent, the subjects were randomly allocated either 10mg alendronate or placebo in a double-blind fashion. All patients received a supplement of 500mg elemental calcium daily. BMD at the lumbar spine, femoral neck, and distal forearm was measured at baseline and 6 and 12 months after treatment. Biochemical markers of bone resorption were determined at baseline and 6 months after treatment. Baseline characteristics were similar in both alendronate- and placebo-treated groups. Ten subjects discontinued the study. Of 70 subjects, 32 received 10mg alendronate daily and the remaining subjects received placebo. At 1 year, BMD in the alendronate-treated group had increased from baseline by 9.2%, 4.6%, and 3.1% at lumbar spine, femoral neck, and distal forearm, respectively. These percentages were greater than those in controls (4.1%, 0.6%, and 1.0%, respectively). Urinary N-terminal telopeptide (NTx)-I and serum C-terminal telopeptide (CTx)-I levels decreased in both groups after 6 months of treatment. However, more reduction was demonstrated in the alendronate-treated group (71.9% vs. 28.4%, P 0.01, and 84.7% vs. 33.1%, P 0.01, respectively). Compliance with treatment and drug tolerability were good in both alendronate and placebo groups. We concluded that treatment with alendronate 10mg daily for Thai postmenopausal women with osteoporosis significantly increased BMD at all skeletal sites and reduced biochemical markers of bone resorption. It was well tolerated without any serious side effects.     

Comparison of spine and femur reference data in native Chinese women from different regions of China

The aim of this study is to explore the differences of BMD reference curves at various skeletal sites among Chinese women from different regions of China and to investigate the feasibility of establishing a unified national BMD reference database for Chinese women. We measured BMD at the posteroanterior (PA) lumbar spine, femoral neck, trochanter and Wards triangle by dual-energy X-ray absorptiometry bone densitometer in 3,422 Changsha women of South Central China, aged 20–84 years. The documented BMDs of reference populations of women in all other areas included Shanghai ( n =2,111) and Nanjing ( n =3,174) in the East, Shenyang ( n =1,213) in the Northeast, Kunming ( n =523) in the Southwest, Chongqing ( n =811) in the Midwest and Xian ( n =1,320) in the Northwest. We adopted the cubic regression as the fitting model for reference curves of BMD that varied with age, conducted conversions of BMD measured by various bone densitometers from different manufacturers and compared the differences between standardized BMD (sBMD) reference curves and combined ones for women from different areas. Our results revealed that by comparing variances in women from different areas, the average variances of non-standard BMD were 0.8–30.8% at the PA spine, 0.7–24.5% at the femoral neck, 0.6–29.9% at the trochanter and 1.1–54.7% at Wards triangle, while average variances of sBMD either significantly decreased or disappeared (0.8–3.9% at the PA spine, 0.7–8.6% at the femoral neck, 0.6–8.3% at the trochanter and 1.1–29.9% at Wards triangle). The sBMD reference curves were highly positive-dependent with combined ones ( r =0.913–0.999, P =0.000). At the PA spine and trochanter, the effect of combined sBMD curves presented well in women from different areas, except for those from Shanghai at the PA spine and Shenyang at the trochanter, indicating that sBMD curves were significantly different from pooled ones; at the femoral neck and Wards triangle, the effect of combined sBMD reference curves was poor, indicating that sBMD curves demonstrated significant differences from pooled ones in women from a majority of these areas. We conclude that, in high density population areas, sBMD reference curves showed no significant geographic differences in women from various regions. In women from different areas, sBMD reference curves present good pooled results at the PA spine and trochanter. The less ideal combining effect of the sBMD curves at both femoral neck and Wards triangle might be caused by the intrinsic differences from the different measuring instruments.     

Factors influencing metacarpal bone mineral density in adults with cerebral palsy

Several studies have examined bone mineral density (BMD) and related factors in children with cerebral palsy, but there are no such studies of adults with cerebral palsy. We evaluated BMD in 123 institutionalized adults (51 men aged 21–41 years and 72 premenopausal women aged 24–46 years) with cerebral palsy, and examined the associations of BMD with mobility level, use of anticonvulsant drugs, and abnormal calcium metabolism status. Hand radiographs were used to measure BMD of the second metacarpal bone (mBMD). Body weight (kg), height (m), and body mass index (BMI) were recorded. Serum calcium, phosphate, and alkaline phosphatase were measured. Abnormal calcium metabolism, defined as calcium 8.5mg/dl, phosphate 2.6mg/dl, or alkaline phosphatase 260U/l, was identified in 28% of the men and 31% of the women. Multiple regression analysis showed that the use of anticonvulsant drugs was significantly associated with lower mBMD in both sexes. Higher alkaline phosphatase level was significantly associated with lower mBMD in men. Mobility level (ambulation) was significantly associated with higher mBMD in women. Neither age nor BMI correlated with mBMD. Our findings indicated poor bone health status in adults with cerebral palsy and the existence of several factors that could affect bone metabolism in these patients.     

The Risk of Colles’ Fracture is Associated with the Collagen I Alpha1 Sp1 Polymorphism and Ultrasound Transmission Velocity in the Calcaneus Only in Heavier Postmenopausal Women

To compare the ability of the bone mineral density (BMD) at the distal forearm, collagen I alpha 1 (COLIA1) polymorphism, and ultrasound stiffness to identify individuals with increased risk of wrist fracture, we studied 183 postmenopausal Czech women with a wrist fracture and 178 postmenopausal controls, ages 45–70 years. The genotypes Ss and ss were significantly overrepresented among fracture cases. The BMD measurements at the femoral neck, total femur, and distal forearm as well as ultrasound stiffness of the heel, broadband ultrasound attenuation (BUA), and speed of sound (SOS) were significantly lower in the fracture cohort. BMD of the distal forearm was the main determinant of susceptibility to the wrist fracture. Weight, the COLIA1 genotype, and ultrasound SOS further strengthened the predictive value of BMD. However, we found interaction between weight and both the COLIA1 Sp1 polymorphism and ultrasound parameters. Presence of the s allele as well as low SOS acted as significant predictors of wrist fracture only in heavier women, (62 kg) but not in women with a body weight of less than 62 kg. In heavier women, both the COLIA1 Sp1 polymorphism and ultrasound parameters acted as independent markers that contributed to BMD to enhance fracture prediction. However, the COLIA1 enabled a higher specificity (specificity 72.4%, sensitivity 44.2%), whereas SOS enabled a higher sensitivity (sensitivity 73.9%, specificity, 45.7%). We conclude that BMD at total forearm, the COLIA1 polymorphism, and ultrasound SOS are independent predictors of wrist fracture in postmenopausal women. The effect of the COLIA1 Sp1 polymorphism and SOS on wrist fracture risk is more pronounced in patients with a higher body weight.     

Bone mineral density in women with sarcoidosis

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Almost any organs of the body, but mostly the lungs, are involved. Bone mineral density (BMD) can be affected directly or indirectly in chronic granulomatous systemic diseases such as sarcoidosis. The aim of our study was to evaluate BMD in premenopausal and postmenopausal sarcoidosis patients with or without prednisone treatment and to compare their BMD values with those of a control group having the same menopausal status. Thirty-five premenopausal women (18 untreated, 8 treated, and 9 controls) and 21 postmenopausal women (5 untreated, 5 treated, and 11 controls) were included in the study. All of the patients had a histologically proven diagnosis and were being followed-up at the Sarcoidosis Outpatient Clinic of our unit. BMD of the lumbar (L) spine and femoral neck was measured by dual-energy absorptiometry (DEXA). The subgroups of premenopausals and postmenopausals were compared separately. Comparison among the groups was performed by using analysis of variance. Age, duration of the disease, and body mass index were comparable in treated, untreated, and control subgroups of the pre- and postmenopausal groups, and the subgroups of postmenopausals had comparable durations since menopause. For premenopausals, BMD values at L1–4 were not significantly different among the subgroups (0.920 ± 0.08g/cm², 0.801 ± 0.09g/cm², and 0.910 ± 0.05g/cm², for untreated, treated, and controls, respectively). However, the BMD value at the femoral neck in treated patients (0.921 ± 0.1g/cm²) was significantly lower than the values in untreated patients (1.080 ± 0.2g/cm²; P 0.01) and in controls (1.028 ± 0.17g/cm²; P 0.05). For postmenopausals, the BMD value at L1–4 in controls (1.019 ± 0.07g/cm²) was significantly higher than the values in untreated patients (0.783 ± 0.01g/cm²) and in treated patients (0.751 ± 0.08g/cm²; P 0.001 for both). The BMD value at the femoral neck in controls (0.890 ± 0.1g/cm²) was higher than the values in untreated patients (0.745 ± 0.08g/cm²) and treated patients (0.747 ± 0.1g/cm²), but the difference was not statistically significant (P = 0.06). We concluded that sarcoidosis patients, especially postmenopausal patients with corticosteroid treatment, may have an increased risk of bone mineral loss. Large-scale studies are warranted in order to delineate the exact roles of the disease itself, menopausal status, and corticosteroid treatment in this bone mineral loss.     

Potentiation of transforming growth factor (TGF-β1) by natural coral and fibrin in a rabbit cranioplasty model

The association of a biodegradable material and a growth factor could be of clinical value for treating bone defects. We therefore tested the association of transforming growth factor (TGF-1) in fibrin glue and coral granules to heal skull defects in rabbits. Adult rabbits underwent a double trepanation symmetrically in both parietal bones. Using histomorphometry, we compared bone repair after 1 month in control animals (n=5) and in animals treated with either TGF-1 as a single injection of 1 g in methylcellulose (n=5) or in fibrin glue (n=5), or with coral granules in fibrin glue (n=4) or with coral granules and TGF-1 1 g in fibrin glue (n=5). We measured the diameter of the remaining defect and the surface of the bone growth. TGF-1 without coral in either methyl cellulose or fibrin induced a partial closure of the defect as assessed by a significant decrease in the defect diameter, compared with the control group. However, the association of TGF-1 in fibrin and coral induced an area of the bone growth higher than in any other groups (P<0.05). Two months after surgery, this triple association induced a better healing of the defect than coral alone or control group. In each group treated with TGF-1, the mineralization rate was increased not only at the treated side but also in the contralateral defect which was untreated, suggesting a diffusion of the growth factor. Indeed, when pooled together, the diameter of the defect at the contralateral side of 14 animals that had received TGF-1 was reduced compared with the control group. Significant coral granules resorption occurred between month 1 and 2 and was unchanged by the addition of TGF-1. In conclusion, the triple association of coral granules and TGF-1 in fibrin could be of interest for treating bone defects.     

Role of sex steroids in the regulation of bone morphology in men. The MINOS study

In ageing men, skeletal fragility is associated with reduced cortical thickness and decreased bone density. To better understand the role of testosterone and 17-estradiol regarding these characteristics of skeletal fragility, we correlated their circulating levels with the estimates of mechanical bone properties derived from areal bone mineral density (aBMD) measured by DXA. External diameter and BMD were used to estimate cortical thickness, cross-sectional area (CSA), section modulus, buckling ratio and strength index of the femoral neck and distal radius on 760 men aged 40–85 years. The 17-estradiol level was an independent positive determinant of CSA, aBMD and estimated cortical thickness of both bones. In multivariate models adjusted for age, body weight, height, lean body mass and testosterone concentration, men in the lowest quartile of 17-estradiol had lower CSA at the femoral neck (4.8%, P<0.001) and distal radius (3.6%, P<0.01) compared with men in the highest quartile. They had also thinner cortical bone at the femoral neck and distal radius (4.8%, P<0.001 and 4.6%, P<0.001, respectively). Furthermore 17-estradiol had a negative association with indices of cortical instability (buckling ratio) and a positive association with bending strength (section modulus, strength index) both at femoral neck and radius. Men in the lowest quartile of 17-estradiol had higher buckling ratios (femoral neck 4.8%, P<0.002; radius 5.1%, P<0.005), lower strength index (femoral neck 8.5%, P<0.001, radius 6.1%, P<0.01) and greater section modulus at the femoral neck. However, there were no between-quartile differences in external diameter in any bone sites. Similar, even though somewhat smaller, between-quartile differences were found for bioavailable 17-estradiol. Neither total testosterone nor apparent free testosterone concentration was associated with any bone variables after adjusting for age, body weight, body height, and lean body mass and 17-estradiol level. In conclusion, in elderly men, low concentration of 17-estradiol (total and bioavailable) was associated with a decreased cortical thickness and with a deterioration of biomechanical parameters of long bones (lower section modulus and strength index, higher buckling ratio).Presented in abstract form at the World Congress of Osteoporosis, Lisbon, Portugal, 2002.     

Transforming Growth Factor-β1 Gene Polymorphisms and Bone Turnover,Bone Mineral Density and Fracture Risk in Southern Chinese Women

Genetic contributions play an important role in determining bone mineral density (BMD) and bone turnover. Transforming growth factor- (TGF-) is abundant in bone and has been implicated as an important regulator of both bone formation and resorption. Several polymorphisms of the TGF-1 gene have recently been suggested to be associated with BMD and susceptibility to osteoporotic spine fractures. To determine the relationship between TGF-1 polymorphisms and BMD in southern Chinese women, three SNPs at C^–1348-T, T²⁹-C, and T^861-20-C of TGF-1 gene were analyzed in 237 postmenopausal southern Chinese women by RFLP and direct sequencing. BMD at the lumbar spine and hip region, biochemical markers of bone turnover, as well as serum levels of TGF-1 were measured. Only the T²⁹-C polymorphism of TGF-1 gene was associated with BMD and fracture risk. The prevalence of fragility fractures was significantly higher in individuals with TC genotype (P < 0.05). Serum alkaline phosphatase and osteocalcin levels as well as urinary N-telopeptide excretion were significantly higher in women with TC than with TT or CC genotypes, and the difference remained significant after adjusting for age and BMI (all P < 0.05). Women with TC genotype had lower BMD at the trochanteric (P < 0.03) and total hip region (P = 0.05). No difference was observed in the serum TGF-1 levels among the three genotypes. In conclusion, an association between T²⁹-C polymorphisms of TGF-1 gene and BMD, bone turnover as well as fragility fractures were demonstrated in postmenopausal southern Chinese women.     

Risk of fracture among women who lose bone density during treatment with alendronate. The Fracture Intervention Trial

It is commonly believed that the response to treatment in patients on alendronate is proportional to the increase in bone mineral density (BMD), and that those who lose BMD during treatment might not respond to treatment. In the Fracture Intervention Trial 6,459 women were randomly assigned to treatment with alendronate or placebo; BMD was measured annually, and new spine fractures were assessed by lateral spine films, taken at baseline and end of follow-up. Among subjects who took at least 70% of the study drug (5,220 women), we compared reductions in risk of spine fractures at end of follow-up (3 or 4 years) within various levels of change in total hip and spine BMD after 1 and 2 years of treatment, after adjustment for differences in characteristics between the treatment and control groups. Women losing BMD at the lumbar spine (0% to 4%) while on alendronate had a reduction of 60% in vertebral fracture risk [OR=0.40 (0.16, 0.99)] compared to their counterparts in the placebo group. The few women that lost more than 4% did not have a significant benefit [OR=0.15 (0.02, 1.29)]. Those who gained BMD (0% to 4%) during treatment had a reduction in risk of 51% [OR=0.49 (0.30, 0.78)]. Similarly, women who lost total hip BMD (0% to 4%) during the first year on alendronate had a 53% decreased risk of vertebral fracture compared to their controls taking placebo [OR=0.47 (0.27, 0.81)], whereas those gaining BMD (0% to 4%) had a comparable risk reduction [OR=0.49 (0.34, 0.71)]. This was not observed for the few women who lost more than 4% [OR=0.61 (0.11, 3.45)]. Patients who lost BMD at both the hip and spine were not protected by alendronate. Among patients who adhere to treatment with alendronate, even those who lose BMD benefit from a substantial reduction in risk of vertebral fracture. So, the reduction in bone turnover induced by alendronate might be more important than BMD changes. The few women who lose the most BMD (more than 4% per year) might not benefit from the treatment.This paper was written for the Fracture Intervention Trial Research GroupPresented in part at the 22nd Annual Meeting of the American Society for Bone and Mineral Research, Toronto, Canada, 2000     

Absorptiometry and “osteoporosis”: problems

connecting the dots between diverse clinical and other matters and an updated bone physiology reveals relationships that could modify some ideas about the roles and uses of absorptiometry in osteoporosis work. Herein, absorptiometry means that part of clinical densitometry that depends on X-ray absorption by bone and other tissues, thus excluding ultrasound methods and magnetic resonance imaging. The modifications concern, in part, some limitations of bone mineral density data, the kinds of physiological information that absorptiometry can and cannot provide, the relative importance of bone mass and whole-bone strength, how to define and study bone health and osteoporosis, and two kinds of osteoporotic fractures. As those modifications concern important national health care issues, they deserve answers based on hard evidence. Identifying those modifications might help others to evaluate them.     

Comparative study of nonbridging and bridging external fixators for unstable distal radius fractures

The purpose of this study was to compare nonbridging external fixators (group NB) with bridging external fixators (group B) in the treatment for unstable distal radius fractures. The subjects consisted of 84 patients, 42 in each group. Mean patient age was 64.0 years in group NB and 59.6 years in group B. According to Saitos classification, most fractures were of the comminuted Colles type. No bone graft was made in group NB. Patients of group B showed serious reflex sympathetic dystrophy (RSD). On Saitos evaluation criteria, the proportion of patients evaluated as good or better was 100% in group NB and 95.6% in group B. This finding can be taken as evidence that group NB patients showed better results.     

The effects of calcitonin on bone resorption in hyperthyroidism: a placebo-controlled clinical study

The effects of intranasal calcitonin on bone metabolism were investigated in patients with hyperthyroidism. Urinary deoxypyridinoline (uDPD) levels were measured as a bone turnover marker and lumbar spine (L2) bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA) in 7 patients who were given only antithyroid drug (group 1), in 10 patients who were given antithyroid drug plus intranasal calcitonin (group 2), and in 10 healthy subjects who were given placebo (group 3) at the beginning and at the end of the study. The study continued until the patients with hyperthyroidism became euthyroidic according to the laboratory values. This period was approximately 3 months in groups 1 and 2. At the beginning of the study, uDPD was 21.5 ± 2.6nM DPD/mM creatinine in group 1, 23.3 ± 3.6nM DPD/mM creatinine in group 2, and 4.3 ± 1.2nM DPD/mM creatinine in group 3. uDPD levels measured in groups 1 and 2 were significantly higher than those in group 3 (P 0.001). Area BMD Z scores of the patients in groups 1 and 2 were significantly lower than the healthy controls (P 0.01, for both). At the end of the study, uDPD was 11.5 ± 1.6nM DPD/mM creatinine in group 1, 5.3 ± 0.6nM DPD/mM creatinine in group 2, and 4.4 ± 1.3nM DPD/mM creatinine in group 3. The levels of uDPD obtained in group 1 were significantly higher than those obtained in groups 2 and 3 (P 0.05, for both). The difference between groups 2 and 3 was not significant. Area BMD Z scores measured at the end of the study were found to be increased in groups 1 and 2 compared to early values, but the values were slightly lower than the normal values. In comparison of early and late uDPD values, the decrease in late period was statistically significant in groups 1 (P 0.05) and 2 (P 0.001). We concluded that bone turnover is high in hyperthyroidism. The treatment of hyperthyroidism decreases the rate of bone turnover, but it is not sufficient to prevent the degradation of bone in hyperthyroidism. The addition of intranasal calcitonin to the treatment of hyperthyroidism prevents the degradation of bone.     

Bone mineral density of the spine and femur in healthy Saudis

The reference values of bone mineral density (BMD) were determined in healthy Saudis of both sexes and compared with US / northern European and other reference data. BMD was determined by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femur including subregions: trochanter, Wards triangle, and neck, in 1,980 randomly selected Saudis (age range 20–79 years; 915 males and 1,065 females) living in the Jeddah area. Age-related changes in BMD were similar to those described in US / northern European and Lebanese reference data. Decreases in BMD of males were evident (% per year): 0.3–0.8 (lumbar spine), 0.2–0.4 (femoral trochanter), 0.2–1.4 (Wards triangle), and 0.2–0.7 (femoral neck). Also, decreases in BMD of females were observed (% per year): 0.8–0.9 (lumbar spine), 0.7–0.9 (Wards triangle), and 0.3–0.7 (femoral neck). Using stepwise multiple regressions that included both body weight and height, the former had 2–4 times greater effect on BMD than the latter. Using the mean BMD of the <35-year-old group the T-score values were calculated for Saudis. The prevalence of osteoporosis in Saudis (50–79 years) at the lumbar spine using the manufacturers vs Saudi reference data was 38.3–47.7% vs 30.5–49.6 (P<0.000), respectively. Similarly, based on BMD of total femur, the prevalence of osteoporosis using the manufacturers vs Saudi reference data was 6.3–7.8% vs 1.2–4.7% (P<0.000), respectively. Saudis (50 years) in the lowest quartile of body weight exhibited higher prevalence of osteoporosis (25.6% in females and 15.5% in males) as compared to that of the highest quartiles (0.0% in females and 0.8% in males). The present study underscores the importance of using population-specific reference values for BMD measurements to avoid overdiagnosis and/or underdiagnosis of osteoporosis.