A randomized controlled trial of vitamin D supplementation on preventing postmenopausal bone loss and modifying bone metabolism using identical twin pairs.

Vitamin D supplementation, when given with calcium, has been shown to increase bone mineral density (BMD) and reduce the incidence of hip fracture in elderly subjects. Despite its widespread use, the benefits of vitamin D supplementation in younger women and as a single agent are less clear. We performed a randomized co-twin, placebo-controlled, double-blind trial over 2 years to measure the effect of vitamin D3 supplementation on bone density and bone metabolism in young postmenopausal women. Seventy-nine monozygotic (MZ) twin pairs (mean age, 58.7 years; range, 47-70 years) were recruited. For each twin pair, one was randomized to 800 IU cholecalciferol/day for 2 years and the other was randomized to placebo. BMD was measured at the spine and hip and heel ultrasound at baseline, 12, 18, and 24 months. Samples were collected at 0, 3, and 6 months to measure serum calcium, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, and urinary deoxypyridinoline (DPD). In total, 64 pairs completed the study. No differences in baseline characteristics were seen between the groups. At 6 months, the treatment group had an increase in serum vitamin D [mean +/- SEM intrapair difference, 14.1+/-2.4 microg/liter (p < 0.001)]. There were no significant differences in other serum measurements or bone markers at 3 months or 6 months. At 24 months, no significant treatment effect was seen on BMD or calcaneal ultrasound change within pairs. Subanalysis of treatment response by vitamin D receptor (VDR) genotype revealed no significant difference in effect on BMD variables with treatment. On the basis of these results, vitamin D supplementation, on its own, cannot be recommended routinely as an osteoporosis prevention for healthy postmenopausal women with normal vitamin D levels under the age of 70 years.     

Benefits of milk powder supplementation on bone accretion in Chinese children

Low dietary calcium intake has been demonstrated to be a risk factor for hip and vertebral fractures in studies conducted among Hong Kong Chinese. Few studies have demonstrated the effect of milk supplementation in bone accretion in Chinese children. The aim was to examine the effects of milk powder supplementation in enhancing bone accretion in Chinese children. Three hundred and forty-four children, aged 9–10 years old, were randomized to receive milk powder equivalent to 1300 mg and 650 mg calcium, and to a control group, respectively. Bone mineral density (BMD) at the proximal femur, lumbar spine and total body were measured at 6 months, 12 months and 18 months. The treatment effects were modeled using linear mixed effect models and compared using linear contrast F-tests, by intention-to-treat. Subjects randomized to milk powder equivalent to 1300 mg calcium had significantly higher increase in BMD at both the total hip (7.4±0.4% in treatment group versus 6.3±0.4% in the control) and the spine (8.4±0.5% in the treatment group versus 7.0±0.5% in the control group). Subjects randomized to milk powder equivalent to 650 mg calcium had smaller increases in BMD at the total hip and spine, although the increase in BMD at the total body was significantly higher (3.1±0.3% in treatment group versus 2.4±0.2% in controls). It is concluded that supplementing the diet of Chinese children with milk powder was effective in enhancing bone accretion.     

The effects of calcium supplementation and exercise on bone density in elderly Chinese women

A randomized controlled trial was carried out to determine whether calcium supplementation and load-bearing exercise can increase or maintain bone mass in the elderly. Fifty Chinese women, aged 62–92 years, living in a hostel for the elderly in Hong Kong were randomized to enter one of four treatment groups: (I) calcium supplementation of 800 mg (as calcium lactate gluconate) daily; (II) load-bearing exercise four times a week plus a daily placebo tablet; (III) calcium supplementation daily and load-bearing exercise four times a week; (IV) a placebo tablet daily. The interventions went on for 10 months. The bone mineral density (BMD) was measured at three sites in the hip (femoral neck, Ward's triangle and intertrochanteric area) and the L2–4 level of the spine. The percentage change in BMD in 10 months was used as the main outcome measurement. The parathyroid hormone level and indices of bone metabolism were also measured before and after 10 months of intervention.The BMD at Ward's triangle and the intertrochanteric area increased significantly in subjects on calcium supplement (p<0.05), but there was no significant change at the spine and femoral neck. Exercise had no effect on bone loss at any site. However, the results of two-way analysis of variance showed a significant joint effect of calcium supplements and exercise at the femoral neck (p<0.05), but not at the other sites. The parathyroid hormone levels fell significantly in subjects on calcium supplements (p<0.01).Calcium supplement in the form of calcium lactate gluconate was adequately absorbed in elderly Chinese women with a calcium intake of less than 300 mg per day. It was effective in reducing bone loss at the hip, and there may be interaction effects with exercise in maintaining bone density.     

Nandrolone decanoate and intranasal calcitonin as therapy in established osteoporosis

This study used a randomized, 2 × 2 factorial design to evaluate over 2 years the effect of intranasal salmon calcitonin and intramuscular nandrolone decanoate on bone mass in elderly women with established osteoporosis. The study was double masked in relation to calcitonin and open in relation to nandrolone decanoate. One hundred and twenty-three women aged 60–88 years who had sustained a previous osteoporotic fracture, or had osteopenia, were recruited through an outpatient clinic. Women were assigned to one of four groups: (1) daily placebo nasal spray, (2) 400 IU intranasal calcitonin daily, (3) 20 intramuscular injections of 50 mg nandrolone decanoate (given as two courses of 10 injections) plus placebo nasal spray, or (4) 20 injections of 50 mg nandrolone decanoate plus 400 IU intranasal calcitonin daily. All subjects received 1000 mg calcium supplementation daily. Outcomes measured included changes in bone mineral density (BMD) at the lumbar spine, as measured by dual-energy quantitative computed tomography (DEQCT), in BMD of the proximal femur, and BMD and bone mineral content (BMC) of the lumbar spine and forearm, as measured by dual-energy X-ray absorptiometry (DXA). Significant positive changes from baseline in DXA BMC at the lumbar spine were observed over 2 years in the calcitonin group (5.0±1.9%, mean ± SE) and in the nandrolone deconate group (4.7±1.9%) but not in the placebo group (1.1±2.2%) or the combined therapy group (0.7±1.8%). Modelling based on the 2×2 factorial design revealed that nandrolone decanoate was associated with a 3.8±1.8% (p<0.05) gain in DXA BMD at the proximal femur. Modelling also revealed that calcitonin treatment was associated with a loss of 11.5±4.7% in DEQCT BMD at the lumbar spine and a loss of 3.7±1.8% in DXA BMD at the proximal femur (p<0.05). There was in vivo antagonism between the two medications of 7.9±3.9% for DXA BMC at the lumbar spine. Both agents caused positive changes from baseline in lumbar spine BMC. Nandrolone decanoate had beneficial effects on BMD at the proximal femur. This dose of intranasal calcitonin was associated with deleterious effects on trabecular BMD at the lumbar spine and total BMD at the proximal femur. There may be significant clinical antagonism between these two medications.     

Diet and exercise during growth have site-specific skeletal effects: a co-twin control study

Exercise and improved nutrition offer safe, low-cost and widely applicable approaches to potentially reduce the burden of fractures. We conducted a cross-sectional study of 30 monozygotic and 26 dizygotic male twin pairs, aged 7–20 years to test the following hypotheses: (1) Associations between bone mass and dimensions and exercise are greater than between bone mass and dimensions and protein or calcium intakes; (2) exercise or nutrient intake are associated with appendicular bone mass before puberty and axial bone mass during and after puberty. Total body and posteroanterior (PA) lumbar spine bone mineral content (BMC) and mid-femoral shaft dimensions were measured using dual energy X-ray absorptometry (DEXA). Relationships between within-pair differences in nutrient intake (determined by weighed-food diaries) or exercise duration (determined by questionnaire) and within-pair differences in BMC and bone dimensions were tested using linear regression analysis. In multivariate analyses, within-pair differences in exercise duration were associated with within-pair differences in total body, leg and spine BMC, and cortical thickness. Every-hour-per-week difference in exercise was associated with a 31-g (1.2%) difference in total body BMC, a 10-g (1.4%) difference in leg BMC, a 0.5-g difference in spine BMC and a 0.1-mm difference in cortical thickness ( p <0.01- p <0.1). A 1-g difference in protein intake was associated with a 0.8-g (0.4%) difference in arm BMC ( p <0.05). These relationships were present in peri-pubertal and post-pubertal pairs but not in pre-pubertal pairs. Exercise during growth appears to have greater skeletal benefits than variations in protein or calcium intakes, with the site-specific effects evident in more mature twins.     

Differential action of pamidronate on trabecular and cortical bone in women with involutional osteoporosis

Since osteoporotic fractures are mainly related to the diminution of the bone mineral density (BMD), the effect of pamidronate (3-amino-1-hydroxy-propylidene) 1,1-bisphosphonate on the BMD of the spine, proximal femur and radius shaft was evaluated in an initial cohort of 35 postmenopausal women with at least one vertebral fracture due to involutional osteoporosis.Pamidronate was given continuously during 18 months in a daily oral dose of 4.8 to 6.0 mg/kg supplemented with calcium (1 g/day).BMD — measured by dual photon absorptiometry — increased after one year 5.3±1.0% (P<0.001) in lumbar spine and 5.3±1.5% (P<0.001) over trochanter. However no significant changes were observed in the BMD of the femoral neck, Ward's triangle or in the cortical bone of the radius shaft measured by single photon absorptiometry.Pamidronate also decreased significantly urinary hydroxyproline-creatinine excretion after 6 months and thereafter maintained a plateau. After 18 months of treatment the diminution was 42.6±4.9% (P<0.001).The differing effects of pamidronate on the BMD of lumbar spine and proximal femur might be ascribed to dissimilarities between the proportions of trabecular and cortical bone in these. These results suggest that pamidronate may be prescribed to prevent fractures in cases of involutional osteoporosis with a significant decrease of BMD in lumbar spine and/or trochanter.     

Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin-D-replete elderly patients

The efficacy of calcium (Ca) in reducing bone loss is debated. In a randomized placebo-controlled double-masked study, we investigated the effects of oral Ca supplements on femoral shaft (FS), femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD), and on the incidence of vertebral fracture in vitamin-D-replete elderly. Ninety-three healthy subjects (72.1±0.6 years) were randomly allocated to three groups receiving 800 mg/day Ca in two different forms or a placebo for 18 months. Sixty-three patients (78.4±1.0 years) with a recent hip fracture were allocated to two groups receiving the two forms of Ca without placebo. FS BMD changes in Ca-supplemented non-fractured women were significantly different from those in the placebo group (+0.6±0.5% v –1.2±0.7%,p<0.05). There was no difference in effect between the two forms of Ca. The changes of +0.7±0.8% v –1.7±1.6% in FN BMD of Ca-supplemented women and the placebo group did not reach statistical significance. In fractured patients, FS, FN and LS BMD changes were –1.3±0.8, +0.3±1.6 and +3.1±1.2% (p<0.05 for the last). The rate of new vertebral fractures was 74.3 and 106.2 fractures per 1000 patient-years in Ca-supplemented non-fractured subjects and in the placebo group, respectively, and 144.0 in Ca-supplemented fractured patients. Thus, oral Ca supplements prevented a femoral BMD decrease and lowered vertebral fracture rate in the elderly.     

A prospective study of the effects of 1-year calcium-fortified soy milk supplementation on dietary calcium intake and bone health in Chinese adolescent girls aged 14 to 16

The Chinese diet is low in calcium, including among adolescent girls, with an average intake around 500 mg per day. In this study, we compared the percentage change in bone mineral density and content of the spine and hip region in a 1-year follow-up study between 104 adolescent girls aged 14 to 16 years receiving 375 ml calcium-fortified soymilk supplementation and 95 girls in the control group. The mean percentage changes of bone mineral density/content (BMD/BMC) and standard deviation (SD) at 1 year for the supplementation and control groups were as follows: neck of the femur BMD 2.7±2.94%, 1.8±3.49% (P =0.08); trochanter BMD 3.3±3.27%, 1.6±2.94% (P <0.001); intertrochanter BMD 3.6±3.05%, 2.32±2.95% (P =0.002); total hip BMD 3.1±2.39%, 2.05±2.22% (P =0.001); total hip BMC 3.8±3.05%, 2.6±2.96% (P =0.006). The percent difference between the percentage of bone changes in the supplementation and control groups [100× (soymilk-control)/control] ranged from 45 to 113%. We observed no differences in the spine BMD/C and no differences in changes of height and weight between the soymilk supplementation and control groups, which yielded similar results. Stepwise multivariate regression analysis including height, weight, growth stage, dietary energy, protein, calcium from usual diet and physical activity also showed that supplementation was significantly associated with a percentage increase in BMD/C at the hip. We conclude that 375 ml calcium-fortified soymilk supplementation, or an equivalent of about two glasses, is among the effective strategies for bone acquisition and the optimization of peak bone mass in adolescent girls.     

Sex differences in peak adult bone mineral density

Osteoporotic fractures are more common in women than men. Although accelerated bone loss following the menopause is recognized as of major importance, it is generally considered that a lower peak adult bone mass in females also contributes to their increased risk of osteoporosis in later life. To examine potential sex differences in peak adult bone mass we studied 29 pairs of dizygotic twins of differing within-pair sex in whom the female twin was premenopausal (mean age 37 years, range 21-55). Bone mineral density (BMD, g/cm2) was measured at the lumbar spine and femoral neck by dual-photon absorptiometry; 22 pairs also had BMD measured in the distal and 21 pairs in the ultradistal radius by single-photon absorptiometry. There was no significant difference in usual dietary calcium intake or tobacco consumption between the twin pairs. Consistent with accepted dogma, BMD at both radial sites were higher (+27%) in the males than their female cotwins. In contrast, there was no sex difference (male versus female) in BMD (mean +/- SEM) in the femoral neck (0.96 +/- 0.02 versus 0.97 +/- 0.03), and surprisingly, the females had a greater lumbar spine BMD than their male cotwins (1.19 +/- 0.03 versus 1.26 +/- 0.03, p less than 0.05). This difference was observed despite the fact that the males were taller (p = 0.033). If the femoral neck BMD values in the females were corrected for this difference in BMI, their values (0.99 +/- 0.03 g/cm2) were significantly higher than those in their male cotwin (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of oral pamidronate in preventing bone loss in postmenopausal women

We have performed a 2-year prospective double-masked study to determine whether the bisphosphonate pamidronate can prevent bone loss in postmenopausal women and its optimal dosage regimen. One hundred and twenty-one such women (mean ± SD age 57.6±3.4 years; mean ± SD time since menopause 7.5±3.5 years) were randomized to receive either oral pamidronate (300 mg/day) for 4 weeks every 4 months (group A), oral pamidronate (150 mg/day) for 4 weeks every 2 months (group B) or identical placebo capsules (group C). Bone mineral density (BMD) measurements at the lumbar spine and proximal femur were performed at baseline and at 6-month intervals for 2 years using dual-energy X-ray absorptiometry. BMD at the lumbar spine (L2–4) increased significantly in groups A and B after 2 years of treatment (mean ± SD 2.8±2.1% and 3.0±2.9% respectively, bothp<0.001) but decreased in the placebo group (–1.6±3.1%,p<0.01). Identical results were seen for BMD at the femoral neck, which increased significantly in groups A and B after 2 years of treatment (1.2±2.3% and 1.3±2.9% respectively, bothp<0.05) but decreased in the placebo group (–1.9±3.9%,p<0.05). There were significant differences over 2 years between the groups at all anatomical sites (lumbar spine, femoral neck and trochanteric region, allp<0.001; Ward's triangle,p<0.01). However, there were no significant differences between groups A and B, suggesting that the two treatment regimens were equally effective in conserving BMD. There were, however, marked differences in tolerability between the two treatment regimens: 13 women (34%) in group A withdrew from the study because of side-effects, but only 5 women (12%) in group B, which was comparable with placebo. These data demonstrate that intermittent oral pamidronate will prevent bone loss from the lumbar spine and proximal femur of postmenopausal women, and that the more frequent but lower dose regimen is well tolerated.     

Bone mineral density in children with myelomeningocele: effect of hydrochlorothiazide

Children with myelomeningocele experience difficulty with ambulation, which leads to immobilization and secondary loss of bone mineral density (BMD). In addition, non-ambulatory myelomeningocele patients have higher urinary calcium losses than their ambulatory counterparts. Hydrochlorothiazide (HCTZ) is known to reduce urinary calcium loss and increase BMD in non-myelomeningocele patients with hypercalciuria. This study examines the effect of HCTZ on urinary calcium and BMD in non-ambulatory children with myelomeningocele. Thirteen of 20 non-ambulatory patients with myelomeningocele completed the year-long randomized double-blinded study (placebo = 7 and HCTZ = 6). Evaluation included electrolytes, PTH, osteocalcin, 1, 25-OH vitamin D, urinary pyridinolines/deoxypyridinolines (U_pyr/dpyr), urinary calcium/creatinine (U_Ca/Cr), and forearm BMD (dual X-ray absorptiometry). Follow-up electrolytes were obtained at 1–2, 6, and 12 months and U_Ca/Cr and BMD was obtained again at 12 months. There were no initial differences between the placebo and HCTZ groups. U_Ca/Cr decreased in the HCTZ group after treatment (0.20±0.09 vs. 0.04±0.02, p<0.05). However, forearm BMD (z-scores) after 1 year remained unchanged in both the HCTZ (–5.95±0.98 to –5.86±0.92) and placebo (–7.19±0.69 to –6.67±0.63) groups. While use of HCTZ for 1 year did not affect BMD, it reduced urinary calcium excretion in non-ambulatory children with myelomeningocele.     

Beneficial treatment with risedronate in long-term survivors after allogeneic stem cell transplantation for hematological malignancies

In this prospective randomized study we evaluated the effect of risedronate, an aminobisphosphonate, on bone mass and turnover in patients who had undergone allogeneic stem cell transplant (SCT) for hematological malignancies. Thirty-four patients (18 females, 16 males, age 32±10 years) with bone mineral density (BMD) –1.5 SD as a T-score at least 6 months after SCT were treated with calcium 1 g/day and vitamin D 800 IU/day and randomized to receive (n=17, group 1) or not receive (n=17, group 2) oral risedronate 5 mg/day. The duration of treatment was 12 months. After 6 months, lumbar BMD increased by 4.4±1.6% in patients of group 1 and decreased by 4.3±1.5% in those of group 2 (P<0.05); at the femoral neck, BMD did not change significantly in patients of group 1 (+1.2±1.2%), while it decreased in those of group 2 (–4.3±2.1%; P<0.05). After 12 months, lumbar BMD further increased (+5.9±1.7%, P<0.05), compared to baseline in group 1 and slightly increased (+1.1±1.4%) in group 2. No further changes were observed at femoral neck in both groups. In conclusion, treatment with risedronate for 12 months increased BMD significantly at the lumbar spine and prevented further bone loss at the femoral neck in long-term survivors after allo-SCT.     

Positive effect of alendronate on bone mineral density and markers of bone turnover in patients with rheumatoid arthritis on chronic treatment with low-dose prednisone: a randomized, double-blind, placebo-controlled trial

Introduction Alendronate has been described to have a bone-sparing effect in patients treated with moderate and high dosages of prednisone for heterogeneous diseases, however no data are available on groups of patients with the same underlying diseases who receive chronic low-dose prednisone treatment. The objective of the investigation reported here was, therefore, to study the effect of alendronate on bone mineral density (BMD) of the lumbar spine and hips in patients with rheumatoid arthritis (RA) who are on chronic low-dose prednisone treatment. Methods A total of 163 patients with RA, according to the ACR-criteria, were enrolled in a double-blind, placebo-controlled trial. The patients were treated with low-dose prednisone (≤10 mg/day) for at least 3 months. The patients were randomized to receive daily doses of alendronate or placebo: men and premenopausal women received 5 mg alendronate (or placebo) daily; postmenopausal women received 10 mg alendronate (or placebo) daily. All patients received daily calcium (500 mg, or 1000 mg, depending on baseline dietary calcium intake) and vitamin D₃ (400 IU) supplementation. BMD of the lumbar spine (L1–L4) and the (total) hip was measured at baseline and after 6 and 12 months. The primary endpoint was change in BMD of the lumbar spine after 12 months (ITT). At baseline and after 3 and 12 months, serum bone-specific alkaline phosphatase (BAP) and urinary excretion of N-telopeptide (NTX) were measured. Radiographs of the thoracic and lumbar spine were made at baseline and after 12 months and subsequently scored for vertebral deformities. Results The groups were comparable at baseline in age, gender, daily dosage of prednisone, BMD at the spine and the hip and markers of bone turnover, while the number of patients with prevalent vertebral deformities was slightly higher in the alendronate-treated patients (54% versus 39%, not significant). After 12 months, BMD at the lumbar spine had increased by 3.7% in the alendronate-treated patients and decreased by –1.0% in the placebo-treated patients (p<0.0001); at the hip, the changes were +1.0% and –0.1%, respectively (not significant). After 3 months, serum BAP had decreased by 16.9% in the alendronate group versus 3.3% in the placebo group (p=0.0005), while urinary NTX had decreased by 46.4% in the alendronate group versus 12.1% in the placebo group (p<0.0001). After 12 months, no statistically significant difference was found between the groups with respect to number of patients with incident vertebral or non-vertebral fractures. Adverse effects were relatively common in these patients with severe RA: adverse effects were observed in 68% of the alendronate-treated patients and in 73% of the placebo patients (not significant), while serious adverse events were observed in 13% and 17%, respectively (not significant). Conclusion We observed a favourable effect of alendronate on the BMD of the lumbar spine and on the markers of bone turnover in patients with RA treated with low-dose prednisone. These data support the conclusion that the prescribing of alendronate is not only beneficial in patients treated with high-dose prednisone but also in RA patients chronically treated with low-dose prednisone. This trial was financially supported by a grant from MSD, The Netherlands     

Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass

Ipriflavone (IP) (7-isopropoxyisoflavone), a synthetic isoflavone derivative, is active in both inhibiting bone resorption and enhancing osteoblast function. This property suggested its clinical use in the treatment of involutional osteoporosis, and in the prevention of postmenopausal bone mass loss. Forty postmenopausal women with low bone mineral content were enrolled and randomly treated for 12 months with IP 600 mg/day or placebo (PL), according to a double-blind, parallel group design. All patients wee also given an oral calcium supplementation (1 g/day). Bone mineral density (BMD) was measured at the spine (L₂–L₄) by dual-energy X-ray absorptiometry. Bone metabolism markers (serum calcium, phosphate, osteocalcin, and alkaline phosphatase, and urinary calcium, phosphate, and hydroxyproline) were assessed at the same times. After 12 months, a reduction of BMD was evidenced in the PL-treated group, at both the spine (–2.2%, P<0.01 vs baseline) and the forearm (–1.2%). In the IP-treated group, an increase of BMD was obtained (+1.2%, P<0.01 vs placebo, at the spine; +3%, not significant, at the forearm). Bone markers were in the normal range for postmenopausal women; no statistically significant modificantions were observed during the treatment period. Three patients were withdrawn from the treatment in the IP-treated group, and two in the PL-treated group for gastrointestinal disturbances. In the other women, the tolerance of the drug was good and the complicance with the oral treatment was excellent.     

Genetic determination of variation and covariation of bone mineral density at the hip and spine in a Chinese population

Bone mineral density (BMD) is a significant determinant of risk for osteoporosis. Genetic factors are known to account for a major proportion of variation of BMD in Caucasians. However, the degree of genetic determination of BMD in Chinese populations has seldom been investigated. The aim of our study was to investigate the magnitude of the genetic determination of BMD at the spine and hip, and their genetic covariation, in a population of Shanghai city in P. R. China. The subjects consisted of 44 full-sib pairs of females aged 19–43 years, 186 mother-daughter pairs, and 270 nuclear families. For BMD at the spine and hip, the values for narrow-sense heritability h ² (±SE) were 0.72 ± 0.14 and 0.87 ± 0.14, respectively, when estimated by full-sib pairs, and 0.44 ± 0.07 and 0.77 ± 0.07, respectively, when estimated by mother-daughter pairs. There was a significant genetic correlation r _g (±SE) of BMD between the spine and hip, of 0.97 ± 0.01 and 0.76 ± 0.04, respectively, when estimated by full-sib pairs and mother-daughter pairs. The common household impact on BMD in our study was negligible according to the statistical estimate. We conclude that genetic factors play a major role in the determination of the variation and covariation of BMD at the spine and hip in our Chinese sample.     

Bone health in urban midlife Malaysian women: risk factors and prevention

The aim of this study was to identify risk factors associated with osteoporosis in urban midlife Malaysian women and to assess the effectiveness of lifestyle intervention in bone loss prevention with hormone replacement therapy (HRT) as a positive control. A total of 514 disease-free, uterus-intact, non-HRT-using women aged 45 years and older were recruited into the study. After initial bone mineral density (BMD) assessments, they were randomized into three groups: GI (control), G2 (lifestyle intervention), and G3 (lifestyle intervention with HRT). The study group was composed of 67.5% Chinese, 27.8% Malay, and 4.2% Indians with a mean age of 51.07±5.28 years. Two-fifths were postmenopausal, and the prevalence of osteoporosis was 24.1%, seen predominantly at the hip. Postmenopausal women had significantly lower mean BMD and a higher incidence of osteoporosis compared with the premenopausal women, 42.1% vs. 11.1% (p<0.0005). A lower incidence of osteoporosis was found in women who took calcium supplementation regularly as opposed to those who do not, 18.7% vs. 29.3% (p=0.036). Age and a greater postmenopausal duration showed a significant negative association with BMD, whereas higher family income, weight, body mass index, and waist and hip circumference were positively correlated. After 18–20 months, the effect of intervention was assessed based on BMD values of 279 women at baseline and after intervention. Lifestyle intervention alone was effective in premenopausal women, preventing over 90% of spinal bone loss compared with the controls, who lost 11.6% (0.046 g/cm²) bone mass with similar losses of hip bone, 2.0% (0.026 g/cm²) vs. 1.5% (0.020 g/cm²). Premenopausal women on HRT also showed a substantial decrease in spine and hip BMD, 18.6% (0.081 g/cm²) and 9.0% (0.122 g/cm²), respectively. The lifestyle intervention program retarded postmenopausal bone loss by 21% and 37% compared with controls, who lost 9.6% (0.141 g/cm²) and 6.0% (0.138 g/cm²) bone mass at the spine and hip. In comparison, lifestyle intervention with HRT increased postmenopausal BMD by 12.7% (0.216 g/cm²) at the spine and 1.9% (0.042 g/cm²) at the hip. The changes in hip BMD were influenced by current age, ethnicity, and income, while intervention had the strongest effect on spine BMD changes. In conclusion, lifestyle intervention prevented spinal bone loss in premenopausal women and retarded postmenopausal spine and hip bone loss compared with controls. The benefits of physical activity on spine and hip BMD highlight its potential as a safe and cost-effective alternative to HRT, which is not advocated because of its potential adverse effects.     

Sodium monofluorophosphate increases vertebral bone mineral density in patients with corticosteroid-induced osteoporosis

Corticosteroid-induced osteoporosis, which particularly affects the axial skeleton and the proximal femur, is characterized by a state of low bone remodelling. Fluoride is a potent stimulator of trabecular bone formation which could potentially be useful in the treatment of corticosteroid-induced osteoporosis. We investigated the effects of sodium monofluorophosphate (26 mg/day of fluoride) combined with 1000 mg of calcium (MFP-calcium-treated group), or of calcium alone (control), given for 18 months, on bone mineral density (BMD) of lumbar spine (LS), femoral neck (FN) and midfemoral shaft (FS) in 48 patients with corticosteroid-induced osteoporosis. Mean ages were 49.4±3.1 and 51.6±3.0 years (mean± SEM), duration of corticosteroid therapy 7.5±1.8 and 9.3±1.7 years, and mean daily dose of prednisone 18.2±2.3 and 12.1±1.1 mg in the MFP-calcium-treated group and controls, respectively. Initial BMDs (expressed as theZ-score, i.e. the difference in standard deviations from age- and sex-matched normal subjects) were –1.5±0.2 and –1.2±0.2 for LS, –1.4± 0.2 and –1.3±0.2 for FN, and –0.8±0.3 and –0.6±0.3 for FS, in the MFP-calcium-treated group and controls, respectively. Analysis by linear regression of 6-monthly measurement values revealed BMD changes of +7.8 ±2.2 versus + 3.6±1.3% (p<0.02) for LS, –1.5±1.8 versus +0.9 ±1.8% for FN, and –1.1±1.1 versus –0.5±1.4% for FS after 18 months of follow-up in the MFP-calcium-treated group and controls, respectively. For comparison, 17 patients with idiopathic osteoporosis (mean age 63.9±2.0 years), with initial BMDs of –1.3±0.4, –1.6±0.3 and –0.8±0.4 (Z-score for LS, FN and FS, respectively), received MFP and calcium for 22.1±1.7 months. BMD changes in idiopathic osteoporosis were +9.3±2.7% (p<0.005), –1.3±2.0% and +0.6± 0.9% for LS, FN and FS, respectively. These results indicate that the combination sodium monofluorophosphate and calcium was more efficient than calcium alone in increasing lumbar spine BMD in patients with corticosteroid-induced osteoporosis; neither femoral neck nor femoral shaft BMD was affected. Moreover, these effects were similar in patients with corticosteroid-induced and idiopathic osteoporosis.     

Evidence that Treatment with Risedronate in Women with Postmenopausal Osteoporosis Affects Bone Mineralization and Bone Volume

Risedronate is used in osteoporosis treatment. Postmenopausal women enrolled in the Vertebral Efficacy with Risedronate Therapy trial received either risedronate (5 mg/day) or placebo for 3 years. Subjects received calcium and vitamin D supplementation if deficient at baseline. Lumbar spine bone mineral density (BMD) was measured at baseline and at 3 years. Quantitative back-scattered electron imaging (qBEI) was performed on paired iliac crest biopsies (risedronate, n = 18; placebo, n = 13) before and after treatment, and the mineral volume fraction in the trabecular bone was calculated. Combining dual-energy X-ray absorptiometric values with the mineral volume fraction for the same patients allowed us to calculate the relative change in trabecular bone volume with treatment. This showed that the effect on BMD was likely to be due partly to changes in matrix mineralization and partly due to changes in bone volume. After treatment, trabecular bone volume in the lumbar spine tended to increase in the risedronate group (+2.4%, nonsignificant) but there was a significant decrease (−3.7%, P < 0.05) in the placebo group. Calcium supplementation with adequate levels of vitamin D led to an ∼3.3% increase in mineral content in the bone material independently of risedronate treatment. This increase was larger in patients with lower matrix mineralization at baseline and likely resulted from correction of calcium/vitamin D deficiency as well as from reduced bone remodeling. Combining BMD and bone mineralization density distribution data show that in postmenopausal osteoporosis 3-year treatment with risedronate preserves or may increase trabecular bone volume, unlike placebo. This analysis also allows, for the first time, separation of the contributions of bone volume and matrix mineralization to the increase in BMD.     

Polymorphism at an Sp1 Binding Site of COL1A1 and Bone Mineral Density in Premenopausal Female Twins and Elderly Fracture Patients

Polymorphism at an Sp1 binding site in the COL1A1 gene has been reported to be associated with bone mineral density (BMD) and osteoporotic vertebral fracture. We therefore examined for associations and linkage of the Sp1 polymorphism in the COL1A1 gene and BMD at the lumbar spine and femoral neck in 38 monozygotic (MZ) and 40 dizygotic (DZ) twin pairs of white adult women. All twins were premenopausal with an age range of 21–49 years. Sp1 genotypes of 56 patients with idiopathic osteoporotic vertebral fracture were examined for a preponderance of either genotype relative to our normal healthy twin subjects. In the twin sample no significant association was found between Sp1 genotypes and BMD at the spine and femoral neck. No linkage of Sp1 genotype and BMD at the spine or femoral neck was observed in DZ twins discordant for genotype. Frequencies of Sp1 genotypes were similar in our healthy (twin) and fracture population samples. In conclusion, in our American sample of premenopausal twins we found no association or linkage of the Sp1 polymorphism at the COL1A1 gene and BMD at the lumbar spine and femoral neck, and no over-representation of any Sp1 genotype was observed in our sample of patients with osteoporotic vertebral fracture. Taken together these results indicate that the Sp1 polymorphism is not related to BMD in our American sample, and contrasts with the findings in a British population. Received: 16 November 1997 / Accepted: 12 June 1998     

Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate.

We investigated the effects of 18 months of treatment with teriparatide in patients previously treated with long-term antiresorptive therapy using bone turnover markers and bone densitometry. Previous raloxifene treatment allowed for teriparatide-induced early bone marker and BMD increases comparable with previously published results for treatment-n?ive patients. Conversely, previous alendronate treatment reduced the bone marker and BMD response. INTRODUCTION: Teriparatide [rhPTH(1-34)] has been shown to increase BMD and reduce the risk of fracture in postmenopausal women with osteoporosis. Our objective was to investigate the skeletal effects of 18 months of treatment with teriparatide in women whose osteoporosis was previously treated with either alendronate or raloxifene. MATERIALS AND METHODS: Daily subcutaneous injections of 20 microg teriparatide were administered for 18 months to 59 postmenopausal women, 60-87 years of age, with BMD T-scores 相似文献