Physical training preserves bone mineral density in postmenopausal women with forearm fractures and low bone mineral density

Summary One hundred and twelve postmenopausal women with low bone mineral density (BMD) and forearm fractures were randomized to physical training or control group. After one year the total hip BMD was significantly higher in the women in the physical training group. The results indicate a positive effect of physical training on BMD in postmenopausal women with low BMD. Introduction The fivefold increase in hip fracture incidence since 1950 in Sweden may partially be due to an increasingly sedentary lifestyle. Our hypothesis was that physical training can prevent bone loss in postmenopausal women. Methods One hundred and twelve postmenopausal women 45 to 65 years with forearm fractures and T-scores from −1.0 to −3.0 were randomized to either a physical training or control group. Training included three fast 30-minute walks and two sessions of one-hour training per week. Bone mineral density (BMD) was measured in the hip and the lumbar spine at baseline and after one year. Results A per protocol analysis was performed, including 48 subjects in the training group and 44 subjects in the control group. The total hip BMD increased in the training group +0.005 g/cm2 (±0.018), +0.58%, while it decreased −0.003 g/cm2 (±0.019), −0.36%, (p = 0.041) in the control group. No significant effects of physical training were seen in the lumbar spine. A sensitivity intention to treat analysis, including all randomized subjects, showed no significant effect of physical training on BMD at any site. Conclusions The results indicate a small but positive effect of physical exercise on hip BMD in postmenopausal women with low BMD.     

Effect of raloxifene after recombinant teriparatide [hPTH(1–34)] treatment in postmenopausal women with osteoporosis

Summary Loss of bone mineral density occurs after discontinuation of teriparatide, if no subsequent treatment is given. Sequential raloxifene prevented rapid bone loss at lumbar spine and further increased bone mineral density (BMD) at femoral neck, whether raloxifene was started immediately or after a one-year delay following teriparatide treatment. Introduction We compared the sequential effects of raloxifene treatment with a placebo on teriparatide-induced increases in bone mineral density (BMD). A year of open-label raloxifene extended the study to assess the response with and without delay after discontinuation of teriparatide. Methods Following a year of open-label teriparatide 20 μg/day treatment, postmenopausal women with osteoporosis were randomly assigned to raloxifene 60 mg/day (n = 157) or a placebo (n = 172) for year 2, followed by a year of open-label raloxifene. BMD was measured by dual energy x-ray absorptiometry. Results The raloxifene and placebo groups showed a decrease in lumbar spine (LS) BMD in year 2 for raloxifene and placebo groups (−1.0 ± 0.3%, P = 0.004; and −4.0 ± 0.3%, P < 0.001, respectively); the decrease was less with raloxifene (P < 0.001). Open-label raloxifene treatment reversed the LS BMD decrease with a placebo, resulting in similar decreases 2 years after randomization (−2.6 ± 0.4% (raloxifene-raloxifene) and −2.7 ± 0.4% (placebo-placebo). At study end, LS and femoral neck (FN) BMD were higher than pre-teriparatide levels, with no significant differences between the raloxifene-raloxifene and placebo-raloxifene groups, respectively (LS: 6.1 ± 0.5% vs. 5.1 ± 0.5%; FN: 3.4 ± 0.6% vs. 3.0 ± 0.5%). Conclusion Sequential raloxifene prevented rapid bone loss at the LS and increased FN BMD whether raloxifene was started immediately or after a one-year delay following teriparatide treatment. Preliminary data presented previously at the International Osteoporosis Foundation World Congress on Osteoporosis, Toronto Canada June 2–6, 2006, abstract published: Adami S, Munoz-Torres M, Econs MJ, Sipos A, Xie L, Dalsky GP, McClung M, Felsenberg D, Brown JP, Brandi ML, San Martin J. Effect of raloxifene after teriparatide treatment in postmenopausal women with osteoporosis. Osteoporos Int. 2006;17(Suppl 2):S137.     

Biochemical Markers as Predictors of Bone Mineral Density Changes After GnRH Agonist Treatment

To evaluate bone biochemical markers as predictors of the efficacy of a hormone replacement therapy (HRT), we studied the bone changes induced by the cessation and return of ovarian function in 28 patients treated for 6 months with a GnRH agonist. This model reproduced the effects observed in postmenopausal women with high bone turnover treated with HRT. At the end of the treatment, Z scores were 1.8 ± 0.3 for Crosslaps (CTx) and deoxypyridinoline (D-Pyr), and 1.1 ± 0.2 for bone alkaline phosphatase (B-ALP) and osteocalcin (OC). This indicated an imbalance in bone remodeling with a high bone resorption. Bone mineral density (BMD) fell by 4.2 ± 2.5%. The changes in BMD between the 6th and 12th months were 0.34 ± 2.24 and −1.73 ± 3.25% at the lumbar spine and the femoral neck, respectively. Biochemical markers except urinary calcium and hydroxyproline measured at 6 months were positively correlated with the BMD changes at the lumbar spine. After the resumption of menstruation, 13 of 28 women displayed positive spine BMD changes between the 6th and 12th months; in this group, bone biochemical markers measured at 6 months were significantly higher (P= 0.02). Stepwise regression analysis showed that the association of B-ALP and D-Pyr measured at 6 months explained 40% of BMD variance and the association of B-ALP, PTH, and estradiol 56%. We conclude that measuring individual biochemical bone markers can help to predict the bone effect of an increase in the circulating estradiol in women with ovarian deficiency. Received: 16 January 1997 / Accepted: 17 June 1997     

Bisphosphonates in children with hypercalciuria and reduced bone mineral density

Previous studies have demonstrated reduced bone mineral density (BMD) and biochemical changes of excessive bone resorption in some patients with idiopathic hypercalciuria (IH). Consequently, bisphosphonates have been successfully employed in research animals and adults with IH and reduced BMD. We evaluated the effect of treatment with bisphosphonates in seven patients ages 10–16 years with persistent IH and reduced BMD. In five children, preceding traditional therapy failed. All children received oral alendronate and one also IV Zoledronic acid for 6–18 (median 9.0, mean 10.7) months. With treatment, BMD Z scores in the lumbar spine improved from −2.0 ± 0.3 to −0.8 ± 0.8 (p = 0.002) and in the femoral neck from −1.8 ± 0.4 to −0.7 ± 0.9 (p = 0.01); urine N-telopeptides/creatinine decreased from 372 ± 289 to 72 ± 39 nmol/mmol (p = 0.05) and calcium/creatinine from 0.29 ± 0.12 to 0.13 ± 0.06 mg/mg (p = 0.009). Height Z scores, normal at baseline in all, remained unaffected, and no new stones or fractures were documented throughout the treatment period. Serum creatinine, electrolytes, calcium, phosphorus and parathyroid hormone remained normal as well. In summary, in children with IH and decreased BMD, treatment with bisphosphonates normalized urine calcium excretion, eliminated urinary symptoms, and significantly improved reduced BMD. These short-term beneficial effects indicate the need for larger prospective studies on the potential of bisphosphonates to serve as a new tool in treating children with IH and reduced BMD.     

Effects of a combined alendronate and calcitriol agent (Maxmarvil®) on bone metabolism in Korean postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study

Introduction A randomized, double-blind, prospective, 24-week clinical trial was performed to evaluate the effects of a combinative agent, Maxmarvil, of calcitriol (0.5 μg) and alendronate (5 mg) on bone metabolism in postmenopausal women.Methods A total of 217 postmenopausal women with osteoporosis were enrolled; 199 patients were randomly assigned to one of two treatment groups (Maxmarvil group or alfacalcidol group). None of the patients were vitamin-D-deficient, as assessed by serum 25-hydroxyvitamin D (25(OH)D), nor had they received any drugs affecting bone metabolism before enrollment. Bone mineral densities (BMD) of L1–L4 and the femur were measured by dual-energy X-ray absorptiometry (DXA) at the initial assessment and after 6 months of treatment. Serum biochemical assays, including serum calcium, 24-h urinary calcium excretion, and bone turnover markers (both bone-specific alkaline phosphatase [bsALP] and urine N-telopeptide [NTx]), were performed at the baseline and after 3 and 6 months of treatment.Results In the Maxmarvil group, the BMD of the lumbar spine increased up to 2.42±0.5% from the baseline after 6 months (p<0.05). On the other hand, the change in BMD in the alfacalcidol group was 0.28±0.5% after 6 months. There was no significant difference in femoral BMD between the two groups. The levels of bsALP and NTx were significantly lower in the Maxmarvil group than in the alfacalcidol group (−22.04±3.9% vs. −11.42±2.8% [p<0.05] and −25.46±5.2% vs. 1.24±6.2% [p<0.001], respectively). Interestingly, there was a significantly smaller amount of 24-h urinary calcium in the Maxmarvil group (p<0.05).Conclusions Our study demonstrates that a combination of calcitriol and alendronate is quite effective in preventing bone loss, with the advantage of lesser hypercalciuric effect of calcitriol in the postmenopausal osteoporotic women.     

Risedronate for prevention of bone mineral density loss in patients receiving high-dose glucocorticoids: a randomized double-blind placebo-controlled trial

Summary This 6-month randomized double-blind placebo-controlled trial shows that risedronate is well tolerated and effective in improving lumbar spine BMD and reducing loss of BMD at the hips in patients receiving high-dose prednisolone. Introduction Bisphosphonates have proven benefits in patients receiving chronic low-dose glucocorticoids. However, whether they are effective in preventing bone mineral density (BMD) loss during periods of high-dose glucocorticoid treatment is unclear. The objective of this paper is to study the efficacy of risedronate in preventing bone mineral density (BMD) loss in users of high-dose glucocorticoids. Methods Adult patients with medical diseases treated with high-dose prednisolone (>0.5 mg/kg/day) were randomized to receive risedronate (5 mg/day) or placebo for 6 months in a double-blind manner, along with elemental calcium (1,000 mg/day). Changes in BMD were studied. Results One hundred and twenty patients were recruited (82 women, age 42.8 ± 14.3 years, 63% corticosteroid-naive, 30% women postmenopausal) and 103 completed the study. Baseline clinical characteristics and BMD were similar in the risedronate and placebo groups. At 6 months, a significant gain in spinal BMD was observed in the risedronate group (+0.7 ± 0.3%; p = 0.03) but a drop was detected in the placebo group (−0.7 ± 0.4%; p = 0.12). After adjustment for baseline BMD, age, gender, body mass index and cumulative prednisolone dosages, the inter-group difference in spinal BMD remained significant (1.4%; p = 0.006). Both groups had a significant drop in hip BMD, but the magnitude was greater in the placebo arm (−0.8 ± 0.4% in risedronate versus −1.3 ± 0.5% the in placebo). No new fractures developed. Subgroup analysis of corticosteroid-naive patients yielded similar results. Upper gastrointestinal adverse events were numerically more frequent in the risedronate group. Conclusions Risedronate improves spinal BMD in users of high-dose glucocorticoids.     

Fragility fractures and bone mineral density in HIV positive women: a case-control population-based study

Summary This Canadian study of bone health showed that HIV+ women were more likely to have had fragility fractures (OR 1.7) but had BMD values that were not different than women from a national population-based cohort. Introduction Given that 17.5 million women globally are HIV-infected and living longer on anti-retroviral therapy (ART+), it is essential to determine whether they are at risk for osteoporosis as is currently assumed. Methods Assessment of osteoporosis risk factors and lifetime low-trauma (fragility) fracture history used a common interviewer-administered questionnaire and phantom-adjusted bone mineral density (BMD). This study compared HIV+ Canadian women with age- and region-matched control women (1:3) from a national population-based study of osteoporosis. Results One hundred and thirty-eight HIV+ women (100 ART+, 38 ART-) were compared with 402 controls. There were no differences in age (37.7 vs. 38.0 years), BMI (25.0 vs. 26.2), family history of osteoporosis, exercise history, alcohol or calcium intakes, age at menarche, oral contraceptive use or parity. HIV+ cases included more Aboriginal and Black women (12.5% and 16.2 vs. 2% and 1%, respectively), smoked and used injection drugs (53%) more, were more often treated with glucocorticoids, had oligomenorrhea, and reported 10-kg weight cycling. Significantly more HIV+ women reported lifetime fragility fractures (26.1% vs. 17.3; OR 1.7, 95% CI 1.1, 2.6). HIV+ and control women did not differ in BMD: spine 1.0 ± 0.12 vs.1.0 ± 0.14 g/cm² (diff. 0.0, 95% CI −0.27, 0.27) or total femur 0.91 ± 0.15 vs. 0.93 ± 0.12 g/cm² (diff 0.02, 95% CI +0.005, −0.045). Conclusion HIV+ women reported significantly more past osteoporotic fractures than population-based controls despite normal BMD. Research is needed to assess bone microarchitecture and develop a reliable fracture risk assessment tool for HIV+ women.     

Bone ultrasonometry and turnover markers in primary hyperparathyroidism

Quantitative ultrasound (QUS) of bone and new markers of bone remodeling have been poorly investigated in mild primary hyperparathyroidism (PHPT). In this study 26 patients (20 females and 6 males) were evaluated. BUA and SOS were measured by QUS at the heel. Markers of bone remodeling assessed were bone alkaline phosphatase (BAP), osteocalcin (OC), procollagen type I N- and C-terminal propeptides (PINP et PICP), and procollagen type I C-terminal telopeptide in blood and urine (ICTP and CTX). Bone mineral density (BMD) was measured at the lumbar spine (LS), femoral neck (FN), and Ward's triangle (WT). The control group comprised 35 sex- and age-matched subjects. The statistically significant variables between the two groups were (P < 0.05) BUA, BMD_LS, BMD_FN, BMD_WT, BAP, and OC. Corresponding z-scores were −0.55 ± 0.75, −0.66 ± 0.77, −0.66 ± 0.71, −0.67 ± 0.52, 1.87 ± 3.87, and 1.93 ± 3.53, respectively. Although PICP and PINP levels were higher in PHPT patients as compared with controls, the difference was not significant. Several markers of bone turnover were moderately correlated with both QUS (r =−0.39 to −0.55) and BMD (r =−0.48 to 0.63). In conclusion QUS seems to be a relevant tool in the assessment of bone status for patients with mild PHPT. Received: 1 October 1998 / Accepted: 1 July 1999     

Novel, high-frequency, low-strain mechanical loading for premenopausal women with low bone mass: early findings

Universally safe and effective methods of mechanically loading the skeleton to improve strength and prevent fracture have yet to be identified. To be osteogenic, mechanical strains must either be of substantial magnitude or applied at high frequency (>15 Hz). High-magnitude loads place frail bones at risk of fracture. Active loading can rarely be achieved at a frequency faster than 2–3 Hz. A 12-month, uncontrolled, prospective, pilot intervention trial was conducted with five premenopausal Caucasian women with low bone mass. Subjects stood on a vibrating platform (Optimass model 1000 Mechanical Strain Device) and received a 0.2-g stimulus at 30 Hz, 2 × 10 min/day, for 12 months. Bone mineral density (BMD) was measured at the whole body, lumbar spine, proximal femora (PF), and distal radius at baseline and 6 and 12 months by DXA (Hologic QDR-1000/W). Blood and urine were collected at baseline and 3, 6, 9 and 12 months for markers of bone resorption and formation. A mean percent BMD increase of 2.03% ± 0.33% (P < 0.02) was detected at the non-dominant PF after 12 months. Trends for increases were observed at all other sites with the exception of the dominant PF. No uniform trends were observed in bone resorption and formation markers. One subject, on Fosamax, increased BMD by 6% at the lumbar spine and 4.4% at the distal radius. Preliminary findings provide evidence of a possible positive response of regions of low bone mass to brief daily bouts of in-home, passive, noninvasive, low-strain, high-frequency, mechanical loading.     

Effects of additional resistance training during diet-induced weight loss on bone mineral density in overweight premenopausal women

Bone loss accompanies a diet-induced weight loss and could be prevented with a combination of exercises. This study was conducted to examine the effects of additional resistance training during diet-induced weight loss on whole-body and selected regional bone mineral density (BMD). The participants of a 14-week weight-loss study were 42 overweight premenopausal Japanese women who were randomly placed in either a diet-only group (D; n = 21) or a diet plus resistance training group (DR; n = 21). Whole-body BMD and body composition, lumbar spine BMD, and 1/3 radial BMD were measured by dual-energy X-ray absorptiometry before and after the intervention. Bone formation and resorption markers were also measured. Thirty-five participants (83%) completed the study. Individuals in groups D (n = 17) and DR (n = 18) lost 6.2 ± 3.5 kg and 8.6 ± 3.6 kg body weight, respectively. Reductions in percentage fat mass and fat mass in group DR were significantly greater than in group D; lean mass decreased significantly in both groups. The effect of time on whole-body BMD was significant (−0.3%); however, whole-body bone mineral content, lumbar spine BMD, and 1/3 radial BMD remained unchanged. There were no significant timeby-group interactions in the whole-body and regional BMD and bone markers. These results suggest that additional resistance training during weight loss has no effect on BMD in overweight premenopausal Japanese women. Further long-term studies with large numbers of subjects are needed.     

Bone density change and biochemical indices of skeletal turnover

Although biochemical markers of skeletal turnover cannot replace bone density scanning for the diagnosis of osteoporosis, it is thought that they may help add to prediction of fracture risk and help determine adequacy of osteoporosis therapy. Nevertheless, whether biochemical markers in the serum or urine can predict individual rates of bone loss in the spine or hip region is unknown. We studied a heterogeneous group of women (n=81) who were premenopausal, untreated postmenopausal, and estrogentreated postmenopausal with baseline determination of body mass index (BMI), calcium intake, biochemical measurements, and serial bone densitometry over 3 years. Serum assays included bone Gla protein (BGP), total and bonespecific specific included bone Gla protein (BGP), total and bone-specific alkaline phosphatase (AP, BSAP), carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). Urine assays included hydroxyproline (OHP), calcium, total pyridinoline, and total deoxypyridinoline. Individual biochemical markers and calcium intake were modestly correlated with bone density changes but were inconsistent regarding the spine versus the hip. All of the formation variables were significantly correlated to spine density change (r=−0.24 to −0.49) whereas the only resorption variable that correlated was urine OHp/Cr (r=−0.31). The only formation variable that correlated with hip density change was serum PICP whereas all of the resorption variables except serum TRAP were correlated (r=−0.23 to −0.35). “High turnover” individuals were defined as those with levels of biochemical variables at least 1 SD above the mean young normal for each variable. Higher bone loss rates were seen in this group for several of the turnover markers compared with bone loss rates in all other individuals. However, the sensitivity of this “high turnover” status for identifying high bone losers did not exceed 60% for any of the variables. In untreated postmenopausal women, a model using urine OHp, serum ICTP, serum BSAP, and calcium intake was able to predict 42% of the variance of change in BMD of the lumbar spine. A model using BMI, serum ICTP, and serum BGP could predict 32% of the variance of change in BMD of the femoral neck. No combination of markers could predict variance in bone density change at either site in estrogenized women (premenopausal and estrogen-treated postmenopausal). We conclude that measuring individual serum and urine markers of bone turnover cannot accurately predict bone loss rates in the spine and hip; however, combinations of demographic and biochemical variables could predict some of the variance in untreated postmenopausal women. Biochemical markers cannot replace serial bone densitometry for accurate determination of change in bone mass at the most clinically relevant sites.     

骨小梁评分在2型糖尿病患者中评价骨质量的应用

目的探讨骨小梁评分(trabecular bone score,TBS)在评价2型糖尿病患者骨质量中的应用。方法回顾性分析128例2型糖尿病患者和64例非糖尿病患者的腰椎骨密度(bone mineral density,BMD)图像,通过骨小梁评分软件(TBS i Nsight software)计算得出骨小梁评分,分析两组患者的骨密度、骨小梁评分差异,并分析骨小梁评分和骨密度、年龄、体重的关系。结果和非糖尿病组相比,2型糖尿病患者组腰椎BMD升高(0.9103±0.1742 vs 0.8382±0.1422,P=0.005),TBS降低(1.2787±0.122 vs 1.3166±0.1016,P=0.033),在排除年龄、体重、骨密度的干扰后差异依然有统计学意义(P=0.008);相关性分析方面发现TBS和年龄呈负相关(r=-0.395,P0.001),和体质量指数呈负相关(r=-0.270,P0.001); TBS和腰椎BMD呈正相关,非糖尿病患者比糖尿病患者的相关性更强(r=0.563,P0.001 vs r=0.766,P0.001)。结论在2型糖尿病患者中骨小梁评分降低,这和2型糖尿病患者骨折风险增高的事实相符合,骨小梁评分可能成为评估2型糖尿病患者骨质量的指标。     

Association of upper arm circumference at muscle flexion with lumbar spine bone mineral density

We investigated the association of upper arm circumference at muscle flexion with lumbar spine (L2–L4) bone mineral density (BMD) in 252 postmenopausal Japanese women (mean age, 62.0 ± 7.6 years; range, 43–78 years) with right-side dominance. Age, age at menopause, years since menopause (YSM), weight, and height were recorded. Dominant upper arm circumference (cm) was measured at muscle flexion. Lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA). Correlations between BMD and variables were determined using Pearson's correlation coefficient. Significant predictors of the lumbar spine BMD were determined using stepwise multiple regression analysis. Upper arm circumference, weight, and height were positively correlated with BMD (r = 0.397, 0.343, and 0.323, respectively), whereas YSM and age were inversely correlated with BMD (r = −0.415 and −0.392, respectively). On stepwise multiple regression analysis, YSM, upper arm circumference, and weight were significant predictors of BMD (R ² = 0.322, P < 0.0001). Predicted value of the lumbar spine BMD was calculated by the following formula: Predicted BMD = 0.249 − 0.0078 (YSM) + 0.016 (upper arm circumference) + 0.0046 (weight). Dominant upper arm circumference at muscle flexion in combination with YSM and weight is a useful predictor of lumbar spine BMD. Received: July 21, 1998 / Accepted: April 1, 1999     

Effect of Soy Protein on Bone Metabolism in Postmenopausal Japanese Women

We conducted a cross-sectional study of the effects of soybean protein intake on bone mineral density and biochemical markers in 85 postmenopausal Japanese women. Nutrients in the diet of postmenopausal Japanese women visiting the osteoporosis unit, including subjects with normal lumbar spine bone mineral density (L2–4 BMD), were investigated by questionnaire, and the calculated daily energy, protein, soy protein and calcium intake were obtained. L2–4 BMD was measured with dual-energy X-ray absorptiometry, and assays done of serum alkaline phosphatase (ALP) and serum intact osteocalcin (IOC) as bone formation markers and urinary pyridinoline (UPYR) and urinary deoxypyridinoline (UDPYR) as bone resorption markers. Soy protein intake was significantly associated with the Z-score for L2–4 BMD (r= 0.23, p = 0.038) and UDPYR (r =−0.23, p = 0.034). Stepwise multiple regression analyses showed that soy protein intake is significantly associated with the Z-score for L2–4 BMD (β= 0.225, p = 0.04) and UDPYR (β=−0.08, p = 0.03) among four nutritional factors. These results suggest that high soy protein intake is associated with a higher bone mineral density and a lower level of bone resorption, but further studies are needed to confirm the causal dynamic mechanisms. Received: 17 September 1999 / Accepted: 29 February 2000     

Circulating osteoprotegerin and receptor activator of NF-κB ligand system in patients with β-thalassemia major

Osteoporosis represents an important cause of morbidity in patients with β-thalassemia major, and its etiology is multifactorial. Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of the NF-κB ligand (RANKL) system in thalassemia-related bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers of bone turnover, and lumbar spine bone mineral density (BMD) were measured in random samples of males (n = 29; mean age ± SEM, 24.26 ± 1.29 years; range, 13–41 years) and females (n = 31; age, 24.59 ± 0.95 years; range, 12–34 years) with β-thalassemia major and in 30 healthy age-, height-, and weight-matched subjects. Thalassemic patients had significantly lower levels of OPG compared with controls (2.54 ± 0.12 vs. 3.25 ± 0.122, respectively; P < 0.05) and higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 ± 0.03 vs. 0.295 ± 0.046, respectively; P < 0.05). s-RANKL correlated negatively with age (r = −0.3, P < 0.05), and OPG correlated positively with the duration of the interval between the onset of transfusions and chelation therapy (r = 0.52, P < 0.001). Regarding markers of bone metabolism, plasma values of osteocalcin correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s-RANKL ratio (r = −0.55, P < 0.01). In multiple regression analysis only cross-linked N-teleopeptide of type I collagen (NTX) significantly accounted for BMD. Although the OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in β-thalassemia, conventional markers of bone turnover more accurately represent changes in the BMD of these patients.     

Nitrate use and changes in bone mineral density: the Canadian Multicentre Osteoporosis Study

Summary  Nitrates may have beneficial effects on bone. To determine if nitrates were associated with increased bone mineral density (BMD), we conducted a secondary analysis using data from subjects in a prospective study. Subjects reporting nitrate use had increased BMD compared with non-users, confirming that nitrates have positive BMD effects in women and men. Introduction  Prior studies suggest positive associations between nitrates and bone. Methods  We used linear regression models, stratified by gender and adjusted for age, weight, and baseline differences, to determine the association between daily nitrate use and BMD among subjects participating in the Canadian Multicentre Osteoporosis Study. All results are reported as annualised percent change in BMD at the hip and spine among nitrate users compared to non-users. Results  We included 1,419 men (71 reported daily nitrate use) and 2,587 women (97 reported daily nitrate use). Male non-users had decreased hip BMD (−1.3%; 95% confidence interval [95%CI] = −1.6 to −1.1) and increased spine BMD (2.8%; 95%CI = 2.5 to 3.1). Male nitrate users had increased hip BMD (1.4%; 95%CI = 0.1 to 2.8) and spine BMD (4.5%; 95%CI = 3.2 to 5.7). Among women, non-users had decreased hip BMD (−1.9; 95%CI = −2.1 to −1.7) and increased spine BMD (2.1%; 95%CI = 1.9 to 2.4) whilst users had an increase in hip BMD (2.0%; 95%CI = 1.2 to 2.8) and spine BMD (4.1%; 95%CI = 3.4 to 4.9). Conclusion  Nitrate use is associated with increased BMD at the hip and spine in men and women.     

Effect of radiographic abnormalities on rate of bone loss from the spine

Summary When measured by dual-photon absorptiometry (DPA), the adjusted annual rate of change in bone mineral density (BMD) of the lumbar spine was 0.11±0.51 (SE) % in 44 healthy postmenopausal women with radiographic abnormalities in the scan field and −0.97±0.26% in 249 women with normal lateral lumbar radiographs (p=0.046). Rates of loss of BMD from the radius were similar in the 2 groups. Spurious rates of loss of spine BMD are likely to be found in subjects with calcification of the aorta, osteophytes or other abnormalities in the spine scan field. This should be kept in mind when serial spine scans are being considered in these subjects.     

Prediction of bone loss using biochemical markers of bone turnover

Summary 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.     

Classification of osteoporosis in the elderly is dependent on site-specific analysis

Vertebral osteoporosis accounts for over 500,000 spinal fractures annually, the majority of which occur in older women. Despite these statistics, data regarding the rate of spinal bone loss in this population are conflicting. Moreover, the site of skeletal evaluation may significantly alter classification of osteoporosis in this age group. To examine trabecular-rich spinal bone loss with a measurement less affected by age-related artifacts that the AP spine, we measured lateral lumbar spine bone density (BMD) using dual-energy X-ray absorptiometry in 120 healthy, ambulatory, community-dwelling women 65 years of age and older (mean 70±5 years, range 65–88). We also examined cortical-rich sites in the forearm and total body along with AP spine and femoral BMD to assess the impact of site specificity using the World Health Organization (WHO) classification of osteoporosis. Significant losses in BMD were observed at the lateral spine (−1.1%/year,P<0.01), forearm (−0.77%/year,P≤0.01), total hip (−0.75%/year,P≤0.01), femoral neck (−0.70%/year,P≤0.05), and trochanter (−0.78%/year,P≤0.01), but not the AP spine. Using the WHO criteria, lateral spine BMD determinations classified 66% of women with osteoporosis in contrast to 29% using the AP projection. Osteoporosis was diagnosed in 55% of women using measurements of the femoral neck, 43% using the total radius, and 19% using the total body. We conclude that elderly women lose bone at trabecular-and cortical-rich sites (lateral spine and total radius, respectively) in addition to sustaining significant age-related bone loss at mixed cortical/trabecular sites such as the hip. Classification of osteoporosis in this age group more than doubles using lateral versus AP spinal projections, supporting the necessity of developing more uniform agreement on site-specific analyses.     

Effects of Gender and Age on the Association of Apolipoprotein E ε4 with Bone Mineral Density,Bone Turnover and the Risk of Fractures in Older People*

The aim of this study was to examine whether the presence of apolipoprotein E ε4 (ApoE ε4) is associated with a lower bone mineral density (BMD), lower quantitative ultrasound (QUS) measurements, higher bone turnover and fracture risk, and whether these relations are modified by gender and age. A total of 1406 elderly men and women (≥65 years) of the Longitudinal Aging Study Amsterdam (LASA) participated in this study. In all participants, QUS measurements were assessed, as well as serum osteocalcin (OC) and urine deoxypyridinolin (DPD/Cr urine). Follow-up of fractures was done each three months. In a subsample (n = 604), total body bone mineral content (BMC) and BMD of the hip and lumbar spine were measured. In addition, prevalent vertebral deformities were identified on radiographs. In women, the presence of ApoE ε4 was associated with significantly lower femoral neck BMD (g/cm²; mean ± SEM; ε4+, 0.64 ± 0.01 vs. ε4−, 0.67 ± 0.01; p= 0.04), lower trochanter BMD (g/cm²; mean ± SEM; ε4+, 0.58 ± 0.01 vs. ε4–, 0.61 ± 0.01; p= 0.01) and lower total body BMC (g; mean ± SEM; ε4+, 1787 ± 40.0 vs. ε4–, 1863 ± 23.8; p= 0.04). Women with ApoE ε4 also had a higher risk of severe vertebral deformities (OR=2.78; 95%CI: 1.21–6.34). In men, the associations between ApoE status and both hip BMD and QUS depended on age. Only among the younger men (65–69 years) was the presence of ApoE ε4 associated with lower BMD values. Bone markers and fractures were not associated with ApoE ε4 in either women, or men. In conclusion, this large community-based study confirms the importance of ApoE ε4 as a possible genetic risk factor related to BMD and vertebral deformities and demonstrates that its effect is gender related, and depends on age in men only. Received: 6 July 2001 / Accepted: 2 April 2002