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 Three patients were withdrawn from the treatment in the IP-treated group, and two in the PL-treated group for gastrointestinal disturbances.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.     

Exercise maintains bone density at spine and hip EFOPS: a 3-year longitudinal study in early postmenopausal women

It is an important aim in the prevention of osteoporosis to stop or decelerate bone loss during the early postmenopausal years. Here we report on results of the 3-year EFOPS exercise trial in osteopenic women. The exercise strategy emphasized low-volume high-resistance strength training and high-impact aerobics. Forty-eight fully compliant women (55.1±3.3 years) with no medication or illness affecting bone metabolism participated in the exercise group (EG); 30 women (55.5±3.0 years) served as non-training controls (CG). At baseline there were no significant between-group differences with respect to physical fitness, bone mineral density, pain and nutritional status. The training consisted of two group training and two home training sessions per week. The study participants of both groups were individually supplemented with calcium and vitamin D (cholecalciferol). Bone mineral density (BMD) was measured by DXA at the lumbar spine, proximal femur and distal forearm and by QCT at the lumbar spine. Speed of sound and broadband ultrasound attenuation were determined at the calcaneus by quantitative ultrasound (QUS). Pain frequency and intensity at different skeletal sites were assessed via questionnaire. After 38 months, the following within-group changes were measured: DXA lumbar spine, EG: 0.8% n.s.; CG: –3.3% P <0.001; QCT trabecular ROI, EG: 1.1% n.s; CG: –7.7% P <0.001; QCT cortical ROI, EG: 5.3% P <0.001; CG: –2.6% P <0.001; DXA total hip: EG: –0.2% n.s; CG –1.9%, P <0.001; DXA distal forearm, EG: –2.8% P <0.001; CG: –3.8% P <0.001; BUA, EG: –0.3% n.s; CG –5.4% P <0.001; SOS, EG: 0.3% n.s; CG –1.0% P <0.001. At year 3 between-group differences relative to the exercise group were: DXA lumbar spine: 4.1% P <0.001; QCT trabecular ROI: 8.8% P <0.001; QCT cortical ROI: 7.9% P <0.001; DXA total hip: 2.1%, P <0.001; DXA distal forearm: 1.0% n.s.; BUA: 5.8% P <0.05; SOS: 1.3% P <0.001. Pain frequency and intensity in the spine significantly decreased in the exercise group and increased in the control group, while no between-group differences were detected in the main joints. In summary, over a period of 3 years our low-volume/high-intensity exercise program was successful to maintain bone mineral density at the spine, hip and calcaneus, but not at the forearm.     

Effect of intranasal salmon calcitonin therapy on bone mass and bone turnover in early postmenopausal women: A dose-response study

We examine the dose-related effect of intranasal salmon calcitonin (sCT) on the early postmenopausal bone loss and bone turnover; a 2-year, prospective, randomized, double-blind, placebo-controlled study was carried out with 134 healthy women who had passed a natural menopause within 6 months to 3 years. The women were allocated randomly to 2 years of treatment with either 100, 200, or 400 IU of sCT given intranasally or placebo. All groups received a calcium supplement of 500 mg. Twenty-one women left the study before its end and 91 complied with the study criteria throughout. Bone mineral content/density of the distal forearm and lumbar spine and biochemical parameters of bone turnover were measured. Although the measurements after 24 months revealed no significant difference between groups in bone mineral density of the lumbar spine, the average changes over time revealed prevention of bone loss in the groups treated with 200 and 400 IU of sCT (0.2 to-0.6%) and declines of 0.8-1.7% in the groups treated with 100 IU of sCT and placebo (P<0.05–0.01; within-group testing). There was no dose-related response to sCT but there was a significant difference between the pooled groups treated with 200 plus 400 IU of sCT versus the 100 IU sCT and placebo-treated groups (P=0.030–0.005). The same difference between groups was seen for biochemical parameters of bone turnover (P=0.022–0.003). The biochemical parameters of bone turnover revealed decreases of 10–20% (P<0.001; within group testing) in the groups treated with the two highest sCT doses. It was concluded that nasal sCT in doses of 200 and 400 IU has some effect in women soon after the menopause—preventing the bone loss in the spine throughout the first year of therapy and lowering the bone turnover. It may be used as an alternative to hormone replacement when estrogens are contraindicated. The present data indicate that discontinuous strategies should be preferred.     

Effect of Calcium Supplementation as a High-Calcium Mineral Water on Bone Loss in Early Postmenopausal Women

It is generally agreed that an adequate calcium intake is necessary for the maintenance of bone health and that calcium supplementation reduces the rate of bone loss in postmenopausal women. Mineral waters are calorie free, and some, with relatively high calcium levels, might be significant sources of calcium. We studied the effect of mineral water in 45 early postmenopausal women randomly assigned to receive a high-calcium (Ferrarelle, Italy) or a low-calcium mineral water. On the basis of the dietary regimen, women were divided in two clusters (A = 23 subjects, B = 22 subjects) significantly different only for calcium intake (CI) and for dietary consumption of calories (energy). At the end of the study period (13 ± 1 months), bone mineral density at the distal radius showed a significant decrease (P < 0.001) only in cluster with low CI. The difference between the clusters was significant (P < 0.05). Furthermore, the cluster with high CI showed a significant (P < 0.05) reduction in osteocalcin serum levels after 3 months. This study provides further evidence to support the use of a high calcium mineral water as an effective prophylaxis against postmenopausal bone loss. Received: 24 October 1995 / Accepted: 28 January 1996     

Milk supplementation of the diet of postmenopausal Chinese women on a low calcium intake retards bone loss.

The Chinese diet is low in calcium (less than 500 mg/day on average), and previous observational studies have suggested an association between a low calcium intake and risk of hip and vertebral fracture. In this study, we randomly assigned 200 postmenopausal Chinese women (age range, 55-59 years) to receive 50 g of milk powder containing 800 mg of calcium per day or to a control group. The following are the mean percentage changes (and SEs) in height and bone mineral density (BMD) over 24 months: for height, -0.1 +/- 0.2 cm in the milk supplementation group and -0.2 +/- 0.1 cm in the control group; for BMD at the total hip, -0.06 +/- 0.22% in the milk supplementation group and -0.88 +/- 0.26% in the control group; for BMD at the spine (L1-L4), -0.56 +/- 0.29% in the milk supplementation group and -1.5 +/- 0.29% in the control group; for total body BMD, -0.32 +/- 0.16% in the milk supplementation group and -1.2 +/- 0.19% in the control group (p < 0.05 by analysis of covariance [ANCOVA] for repeated measures for height and BMD at all sites). The milk supplementation group had less loss in terms of both height and BMD than the control group (p < 0.05 by ANCOVA for repeated measures). Serum parathyroid hormone (PTH) concentration was lower and serum 25-hyroxyvitamin D [25(OH)D] level was higher in the milk supplementation group than the control group at 12 months (p < 0.05 by paired t-test). We conclude that supplementing the diet of postmenopausal Chinese women with high calcium milk powder retards bone loss.     

Total and regional bone mineral content and fracture rate in postmenopausal osteoporosis treated with salmon calcitonin: A prospective study

Seventy-two postmenopausal osteoporotic women having more than one nontraumatic vertebral crush fracture were studied. Thirty-six of them, aged 68.8±1.2 years (18±4 YSM-years since menopause), were treated with 100 IU/day of salmon calcitonin i.m. plus 500 mg of elemental calcium for 10 days each month. The remaining 36 patients, aged 69.6±1.4 years (19±3 YSM), were given only 500 mg of elemental calcium for 10 days each month. All patients underwent clinical and analytical evaluation every 3 months. Radiological evaluation, assessment of vertebral deformities, and metacarpal radiogrammetry were done every 6 months. Densitometric measurements of total and regional bone mass were made every 12 months. At 24 months, the calcitonin group showed a 60% reduction in the number of new fractures and the group receiving only calcium had a 45% increase (P<0.001). The incidence of vertebral fractures was 0.07 per patient-year in the group treated with calcitonin and 0.45 per patient-year in the group treated with calcium (P<0.001). At 2 years, the calcitonin group showed a 12% increase in cortical bone mass on metacarpal radiogrammetry, a 16% increase in the axial skeleton on trunk densitometry, a 3.5% increase in total body bone mineral content, a 30.7% increase in pelvic bone mineral content, and a 6.2% increase in arm bone mineral content (all P<0.001). In the group treated with calcium alone there was a loss of bone mass in every region. These findings suggest that salmon calcitonin is effective in the treatment of osteoporosis and show that it acts on cortical and trabecular bone.     

Prevention of osteoporosis with nasal salmon calcitonin: Effect of anti-salmon calcitonin antibody formation

The amino acid sequence of salmon calcitonin (SCT) differs considerably from that of the human hormone and specific antibodies (Ab) develop in a significant proportion of patients after parenteral or nasal administration of SCT. Controversy remains regarding the functional importance of these Ab. We report on the development of specific anti-SCT Ab in a population of postmenopausal women receiving nasal SCT for prevention of postmenopausal bone loss, and compare the effects of nasal SCT in women with or without Ab. Thirty-nine per cent of women developed Ab after 6 months of treatment with SCT, 52% after 12 months, and 61% after 18 and 24 months. After 24 months the AB titre was 3.47–17.7×10^–9 M/l (mean ±SD: 13.3±3.1×10^–9 M/l). No significant differences appeared between the changes in lumbar bone mineral density (BMD) measured in the whole population (n=44) (mean±SD: + 1.06±3.9%), the patients without Ab (n=17) (+0.05±3.7%) or in those with Ab (n=27) (+1.7±4.6%). During the same period, a control population randomly assigned to a 500 mg/day calcium intake showed a significant loss of lumbar BMD (–4.57±4.9%) (p<0.01). In conclusion, in healthy postmenopausal women nasal SCT seems to maintain the same preventive effect against bone loss whether or not Ab are present.     

Risk factors for low bone mineral density and the 6-year rate of bone loss among premenopausal and perimenopausal women

Risk factors that are associated with lower bone mineral density (BMD) may not necessarily be associated with increased bone loss among premenopausal and perimenopausal women. We determined risk factors for lower premenopausal and perimenopausal BMD while simultaneously determining risk factors for increased 6-year rate of bone loss among women aged 24–50 years within a population-based prospective cohort study. BMD of the lumbar spine and femoral neck, reported as t scores, were measured five times within the 6-year study among 614 women who were between the ages of 24 and 44 in 1992/1993. Rates of bone loss were calculated from the repeated BMD measurements. Risk factors for lower BMD over time at the lumbar spine included history of any fracture (P=0.005). The major risk factor for lower BMD over time at the femoral neck was family history of osteoporosis (P<0.002). The major protective factor for greater BMD over time at both skeletal sites was additional body weight (P<0.0001). Other protective factors for greater BMD over time at the femoral neck were modest alcohol consumption (P=0.0002) and high-school sports participation (P=0.002). Risk factors for greater bone loss at either skeletal site included postmenopausal status (P<0.0001 at the lumbar spine; P=0.01 at the femoral neck), and the reporting of a reproductive cancer (P<0.0001 at the lumbar spine; P=0.0008 at the femoral neck). Body weight was protective against bone loss at both skeletal sites (P<0.0001). Baseline age, calcium intake, smoking, and current physical activity were not associated with BMD or bone loss. The understanding of the relative importance of risk factors for both low BMD and bone loss may assist in the identification of women at greater risk for subsequent low postmenopausal 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.     

Treatment of postmenopausal vertebral osteopenia with monofluorophospate: A long-term calcium-controlled study

The aim of the present study was to assess the effects of the new fluorine pro-drug monofluorophos-phate (MFP) in postmenopausal women with vertebral osteopenia and high bone turnover. We enrolled postmenopausal women (PMW, 43–59 years) who had had a natural menopause 2–5 years before the study, had vertebral bone mineral density (BMD) <13 SD from the premenopausal mean, and had at least one of the biochemical markers of bone remodeling >1 SD over the mean for premenopausal women. Patients were randomly divided into two treatment groups (group 1, 500 mg/day of oral calcium; group 2, MFP at the dose of 20 mg F-equivalents + 600 mg calcium/day) for 2 years (n=21 in each group). The lumbar vertebral (L2–4) BMD and total body bone mineral (TBBM) were measured by dual-energy X-ray absorptiometry (Lunar DPX, Lunar Corporation, USA). Urinary hydroxyproline excretion (OH-P/Cr), plasma bone Gla protein (BGP) and serum alkaline phosphatase (AP) were assayed. In group 1 the markers of bone turnover and vertebral BMD did not show any significant modification, while TBBM showed a significant (p<0.05) decrease after 24 months. In group 2 a significant (p<0.05) decrease in OH-P/Cr (–23.9±2.0%), and an increase in both BGP (+19.4±2.6%) and AP(+10.3±2.6%) levels were observed after 24 months of MFP administration. In this group, both vertebral BMD (+5.01±0.9%,p<0.01) and TBBM (+4.0±0.6%,p<0.05) showed a significant increase after 24 months. Present results suggest that, in osteopenic PMW, MFP administration induces a significant increase in vertebral BMD without impairment of cortical bone, with a reduction in bone resorption and an increase in bone formation rate.     

Alfacalcidol reduces accelerated bone turnover in elderly women with osteoporosis

To evaluate the effects of alfacalcidol on bone turnover in elderly women with osteoporosis, an open-label, prospective, calcium-controlled study was conducted. A total of 80 patients with osteoporosis were divided into two groups: the control group, group C (mean age, 78.0 years), in which patients were given calcium, and group D (mean age, 77.4 years), in which the patients were given alfacalcidol 1µg/day together with calcium for 6 months. Calcium regulation, lumbar bone mineral density (LBMD), and markers for bone turnover were assessed. A significant increase in urinary calcium/creatinine ratio (90% increase from baseline at 3 months; P = 0.0083, and 60% at 6 months; P = 0.0091) and a significant decrease in serum parathyroid hormone (30% decrease from baseline at 6 months; P < 0.0001) was observed in group D compared with the corresponding changes in group C. Significant decreases of bone resorption markers (deoxypyridinoline and N-telopeptide) at 6 months (about 15% decrease from the baseline values) were observed in group D compared with the corresponding changes in group C. The changes in bone formation markers (bone-derived alkaline phosphatase and osteocalcin) in group D were significantly different at 6 months (–21.5%; P = 0.0047 and –13.4%; P = 0.0032, respectively) from the values in group C. The magnitudes of the decrease in bone turnover markers were highly correlated with the corresponding baseline values, suggesting that alfacalcidol treatment effectively reduces bone turnover in patients with high bone turnover rates. The LBMD in group D increased by 1.7% and that in group C decreased by 1.6% (P = 0.0384). The changes in calcium metabolism and LBMD were in good agreement with those in previous reports. Although the changes in bone turnover markers in group D were slight, significant reduction in bone turnover with alfacalcidol treatment, together with the change in calcium metabolism, may account for the effects of alfacalcidol on BMD and on fracture prevention reported previously. In conclusion, alfacalcidol reduces bone turnover in elderly women with high-bone-turnover osteoporosis, and it may have beneficial effects on bone.     

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 effect of 1-year transdermal estrogen replacement therapy on bone mineral density and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus patients: a randomized,double-blind,placebo-controlled trial

We studied the effect of 1-year transdermal estrogen replacement therapy (ERT) on bone mineral density (BMD) and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus (SLE) patients in a randomized, double-blind, placebo-controlled trial. SLE patients were randomly allocated to treatment (estradiol; 50 g transdermal 17-estradiol; n=15) or placebo (n=17) group. Both groups received 5 mg continuous oral medroxyprogesterone acetate, 500 mg calcium and 400 IU vitamin D₃. L₁–L₄ spine (LS), left femur and total hip BMD were measured at baseline and at 6 and 12 months. Serum osteocalcin (OC) and degradation products of C-terminal telopeptides of type-I collagen (CTx) levels were measured at baseline and 3, 6, 9, and 12 months. There was a significant difference in the percentage change of LS BMD at 6 months between the two groups (103.24±3.74% (estradiol group) vs 98.99±3.11% (placebo group); P<0.005). There was a significant decrease within the estradiol group in the CTx levels between baseline and all subsequent visits (P<0.05). There was no significant difference in SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) damage index and corticosteroid dose during the study period. Transdermal estradiol may prevent bone loss in postmenopausal SLE women at the lumbar spine and femur, with no increase in disease activity among postmenopausal SLE women receiving transdermal ERT. The high dropout rate (8/15) leads us to the conclusion that efficacy of HRT in a high-risk group such as SLE women can be attained only in a small number of patients, provided all inclusion/exclusion criteria are strictly adhered to.     

Relationships Between the Changes of Serum Levels of OPG and RANKL with Age, Menopause, Bone Biochemical Markers and Bone Mineral Density in Chinese Women Aged 20-75

The correlations between the serum levels of OPG, RANKL with age, menopause, bone markers, and bone mineral densities (BMDs) at the lumbar spine and proximal femur were studied in 504 pre- and postmenopausal Chinese women aged 20–75 years. We found that age was positively and negatively correlated with serum concentrations of OPG (r = 0.442, P < 0.001) and RANKL (r = –0.263, P < 0.001), respectively. Compared with premenopausal women, postmenopausal women showed higher serum OPG levels (107.6 ± 3.0 vs 72.0 ± 1.8 pg/ml, P < 0.001), lower serum RANKL concentrations (4.7 ± 0.4 vs. 5.8 ± 0.3 pg/ml, P < 0.001) and RANKL/OPG ratios (0.045 ± 0. 004 vs. 0.099 ± 0.008, P < 0.001). Neither serum levels of OPG nor RANKL or RANKL/OPG ratio correlated with BMDs after adjustment of age and menopause. They also showed no differences among normal, osteopenic and osteoporotic postmenopausal women. Serum levels of OPG were positively correlated with urinary excretion of NTx (r = 0.1453, P = 0.006). Serum levels of RANKL (r = –0.1928, P < 0.001) and RANKL/OPG ratio (r = –0.1303, P = 0.013) were inversely correlated with serum concentrations of OC. In multiple regression analysis, up to 20% variance (R² = 0.106–0.224) of the OPG-RANKL system in peripheral circulation can be explained by age, menopause and bone markers.These results suggest that although serum OPG and RANKL concentrations were unrelated with BMDs, the age– and menopause– dependent changes of serum OPG and RANKL might be a protective mechanism against the accelerated bone loss in postmenopausal women.     

Prevention of bone loss in early nonsurgical and nonosteoporotic high turnover patients with salmon calcitonin: The role of biochemical bone markers in monitoring high turnover patients under calcitonin treatment

Annual bone loss rate was estimated in a group of randomly selected 150 nonsurgical and nonosteoporotic early postmenopausal women, 42–56 years, with the use of the mathematical equation proposed by Christiansen et al. (OSTEOTREND-R) [1]. Fifty-six women were characterized as high turnover patients (estimated annual bone loss more than 2.7%). These high turnover patients were included in a double-blind, placebo-controlled clinical study. Patients were divided into two groups of 28 women each. The first group of patients received 100 IU of salmon calcitonin intranasally daily for 1 year and the second group intranasal spray of placebo daily. Blood and urine biochemical parameters as well as bone mineral content of the spine and proximal forearm were determined initially and at the end of 6 and 12 months. No other side effects were noted apart from discomfort of nasal mucosa in two patients (one in each group). The group of calcitonin-treated patients showed a dramatic decrease in bone loss rate as estimated with the use of biochemical bone markers at the end of 6 and 12 months (3.7% versus 0.8% and 0.0% at the end of 6 and 12 months, respectively, P<0.001) whereas in the placebo group, bone loss rate remained unchanged (4.2% versus 4.1% and 4.3% at the end of 6 and 12 months, respectively). The calcitonintreated patients showed a significant increase in bone mineral content of spine and proximal forearm (P<0.001 at the end of 6 and 12 months, respectively). On the other hand, a significant decrease in all measurement sites appeared in the placebo group. In conclusion, our results showed that nasal salmon calcitonin administration can prevent the increased postmenorpausal bone loss in selected high bone turnover patients. The predicted annual bone loss rate, as estimated with the combination of biochemical bone markers, is useful in monitoring the responsiveness of high turnover patients to calcitonin at short intervals.     

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.     

Effect of impact exercise on bone mineral density in elderly women with low BMD: a population-based randomized controlled 30-month intervention

Evidence of the effect of exercise on bone loss comes mainly from studies in voluntary postmenopausal women, and no population-based, long-term interventions have been performed. The purpose of this population-based, randomized, controlled trial was to determine the effect of long-term impact exercise on bone mass at various skeletal sites in elderly women with low bone mineral density (BMD) at the radius and hip. Participants ( n =160) were randomly assigned to 30 months either of supervised and home-based impact exercise training or of no intervention. The primary outcome measures were femoral neck, trochanter and total hip BMD, and the secondary outcomes were bone density measures at the radius and calcaneum. Outcomes were assessed at baseline, 12 months and 30 months using blinded operators. The analyses were performed on an intention-to-treat analysis. Mean femoral neck and trochanter BMD decreased in the control group [–1.1%, 95% confidence interval (CI) –0.1% to –2.1% and –1.6%, 95% CI –0.4% to –2.7%], while no change occurred in the exercise group. Mean trochanter BMC decreased more in the control group (–7.7%, 95% CI –9.7% to –5.6% vs. –2.9%, 95% CI –5.3 to –0.9). There were six falls that resulted in fractures in the exercise group and 16 in the control group during the 30-month intervention ( P =0.019). A significant bone loss occurred in both groups at the radius and calcaneum. In multivariate analysis, weight gain was associated with increased BMD and BMC at all femur sites both in the exercise group and in the pooled groups. In conclusion, impact exercise had no effect on BMD, while there was a positive effect on BMC at the trochanter. Exercise may prevent fall-related fractures in elderly women with low bone mass.There was no conflict of interest.     

Can biochemical markers predict bone loss at the hip and spine?: A 4-year prospective study of 141 early postmenopausal women

A number of recent studies have suggested that non-invasive measures of bone turnover are associated with bone loss at the forearm in postmenopausal women. Whether bone turnover markers are predictive of bone loss from the clinically important sites of lumbar spine and femoral neck remain unclear, and was the aim of this 4-year prospective study. One hundred and forty-one normal, postmenopausal women (mean age 52.0±3.3 years, mean menopause duration 20.4±5.7 months) were recruited for the study in 1988. Fasting early morning samples of blood and urine were collected at the baseline visit and stored at –20 °C prior to analysis. Serum was assayed for osteocalcin, oestradiol, oestrone, oestrone sulphate, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate and total alkaline phosphatase. Urine was assayed for calcium, hydroxyproline, oestrone glucuronide and the collagen cross-links pyridinoline and deoxypyridinoline using high-performance liquid chromatography. Bone density was measured at the lumbar spine and femoral neck using dual photon absorptiometry at time 0, 12, 24 and 48 months. The mean annual percentage change in bone density (SE) was –1.41% (0.18) at the lumbar spine and –0.86% (0.22) at the femoral neck. There was no evidence of bimodality or a fast loser subgroup as the rates of change were normally distributed. Both simple and multiple stepwise regression analyses revealed no significant correlation between the rates of change in bone density with any biochemical marker, either individually or in combination, despite the study having sufficient power (80%) to detect a correlation of 0.5 between any biochemical marker levels and bone loss. We conclude that single measurements of these markers of bone turnover and endogenous sex hormones appear unlikely to be clinically useful in predicting early postmenopausal bone loss from either the spine or the hip.     

Effects of dietary improvement on bone metabolism in elderly underweight women with osteoporosis: a randomised controlled trial

Malnutrition in elderly people contributes to osteoporosis and fracture. The aim of the study was to investigate the effects of nutritional improvement on bone metabolism in elderly community-dwelling women. A 12-month randomized controlled trial of 71 ambulant women aged 70 years with BMI 21 kg/m² and osteoporosis at the hip was undertaken. They received either calcium (1 g) and vitamin D (800 units of cholecalciferol) only (group 1: n=35) or calcium/vitamin D and one or two cartons of a nutritional supplement drink which provided 300 Kcal, 12 g protein, 11.6 g fat and 36.8 g carbohydrate per carton (group 2: n=36). Body composition and bone mineral density (BMD) were assessed at baseline and 12 months. Biochemical markers of bone turnover were measured at baseline and at 1, 3, 6, 9 and 12 months. Group 2 gained significantly more weight [mean (SD) group 1: 0.15 (2.45), group 2:2.66 (2.8) kg P<0.001] and fat mass [group 1: –0.26 (1.8), group 2:1.9 (1.7) kg P<0.001]. BMD at the spine, femoral neck and total hip did not change significantly, although there was a positive trend at the total hip in group 2 [group 1: –0.5 (5.2), group 2:1.25 (3.3)%, P=0.13]. In a subgroup analysis, irrespective of their treatment group, there was a significant difference in changes in BMD at the lumbar spine and total hip in those who lost body weight (A) compared to those who had maintained or increased their weight (B), [mean (SD) % change in BMD lumbar spine; A: –1.64 (3.75), B: 0.96 (2.75) P=0.013, total hip A: –2.09 (6.0), B: 1.04 (3.3), P=0.05)] A significant reduction in serum CTX, a marker of bone resorption, was seen in group 2 [% decrease at 3 months, group 1: 1 (8.7), Group 2: 32 (5.8), P<0.01]. Serum osteoprotegerin (OPG) increased significantly in group 2 with a maximal increase (27%) observed at 6 (P<0.01) and 9 months (P<0.05). A small increase in bone-specific alkaline phosphatase was seen at 12 months in group 2 [% increase group 1:5 (5), group 2: 17 (6), P=0.05]. Serum osteocalcin increased at 12 months in group 2 (P=0.01). Dietary improvement in elderly women with low BMI is associated with a reduction in bone resorption with a small but "net" positive effect on bone formation.     

Comparison of vitamin D metabolism in early healthy and late osteoporotic postmenopausal women

Summary We studied 20 healthy premenopausal women aged 36.5±4.0 years (mean±1 SD), 123 healthy postmenopausal women aged 50.0±2.4 years, and 103 postmenopausal women aged 65.1±5.6 years with symptomatic osteoporosis (forearm and spinal fracture). Serum levels of vitamin D metabolites [25(OH)D, 24,25(OH)₂D₃, and 1,25(OH)₂D] were compared with (1) bone mass in the forearm (single photon absorptiometry) and in the spine (dual photon absorptiometry); (2) biochemical indices of bone formation (serum alkaline phosphatase, plasma bone Gla protien), and bone resorption (fasting urinary hydroxyproline); and (3) other biochemical estimates of calcium metabolism (serum calcium, serum phosphate, 24-hour urinary calcium, intestinal absorption of calcium). The present study revealed no difference in any of the vitamin D metabolites between the premenopausal women, the healthy postmenopausal women and the osteoporotic women as a group. The concentrations of 1,25(OH)₂D and 25(OH)D were significantly lower in patients with spinal fracture than in those with forearm fracture. In the early postmenopausal women, serum 1,25(OH)₂D was related to forearm bone mass (r=−0.20;P<0.05), intestinal calcium absorption (r=0.18;P<0.05), and 24-hour urinary calcium (r=0.21;P<0.05); serum 25(OH)D was related to spinal bone mass (r=0.23;P<0.01). In the osteoporotic women, serum vitamin D metabolites were not related to bone mass, but 1,25(OH)₂D was related to bone Gla protein (r=0.33;P<0.001), serum phosphate (r=−0.27;P<0.01), and 24-hour urinary calcium (r=0.43;P<0.001). The present study demonstrates that in a population that is apparently not deficient in vitamin D, a disturbance of the vitamin D metabolism is not likely to play a pathogenetic role in early postmenopausal bone loss. Patients with spinal fractures have low levels of vitamin D metabolites, which may aggravate their osteoporosis.