Changes in the serum levels of osteoprotegerin and soluble receptor activator for nuclear factor kappaB ligand after estrogen-progestogen therapy and their relationships with changes in bone mass in postmenopausal women

OBJECTIVE: To investigate changes in the serum levels of osteoprotegerin (OPG) and soluble receptor activator for nuclear factor kappaB ligand (sRANKL) after estrogen plus progestogen therapy (EPT) and to determine their relationships with changes in bone mineral density (BMD) and bone turnover markers in postmenopausal women. DESIGN: Serum levels of OPG, sRANKL, and bone turnover markers, such as osteocalcin and type I C-telopeptide breakdown products, parathyroid hormone, calcitonin, calcium, and phosphorus, and BMD at the lumbar spine and proximal femur were measured in 297 postmenopausal Korean women. In all, 143 women were treated with sequential EPT for 1 year. RESULTS: Before EPT, serum OPG and sRANKL levels and RANKL/OPG ratios were not related to BMD at the lumbar spine and proximal femur, except for a negative correlation (r = -0.13, P < 0.05) between serum OPG and BMD at the trochanter. Of the bone markers, serum parathyroid hormone alone correlated negatively with serum OPG (r = -0.19, P < 0.005) and positively with serum sRANKL (r = 0.23, P < 0.001) and sRANKL/OPG ratios (r = 0.28, P < 0.001). After 6 months of EPT, serum OPG and sRANKL levels were unchanged, but sRANKL/OPG ratios and serum levels of bone turnover markers, such as osteocalcin, type I C-telopeptide breakdown products, and phosphorus decreased significantly. The 1-year change in BMD at the lumbar spine and proximal femur after EPT was not found to be correlated with basal levels of serum OPG, sRANKL, and sRANKL/OPG ratios and their changes at 6 months after EPT. After 6 months of EPT, changes in all bone markers were not associated with changes in circulating OPG, sRANKL levels, and sRANKL/OPG ratios. CONCLUSIONS: After EPT, sRANKL/OPG ratios in the circulation decreased, but changes in this OPG-sRANKL system have no association with changes in any bone marker or BMD. The OPG-sRANKL system in the circulation might be involved in reduced bone resorption after EPT, but does not seem to be clinically useful for predicting BMD or bone turnover status and bone response after hormone therapy.     

Assessment of Denosumab in Korean Postmenopausal Women with Osteoporosis: Randomized,Double-Blind,Placebo-Controlled Trial with Open-Label Extension

PurposeThe efficacy and safety of denosumab was compared with placebo in Korean postmenopausal women with osteoporosis in this phase III study.ResultsBaseline demographics were similar in the 62 denosumab- and 64 placebo-treated subjects who completed the double-blind phase. Treatment favored denosumab over placebo for the primary endpoint {mean percent change from baseline in lumbar spine bone mineral density (BMD) at Month 6 [3.2% (95% confidence interval 2.1%, 4.4%; p<0.0001)]}; and secondary endpoints (mean percent change from baseline in lumbar spine BMD at Month 1, total hip, femoral neck, and trochanter BMD at Months 1 and 6, and median percent change from baseline in bone turnover markers at Months 1, 3, and 6). Endpoint improvements were sustained over 12 months in the open-label extension (n=119). There were no new or unexpected safety signals.ConclusionDenosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a 12-month period in Korean postmenopausal women. The findings of this study demonstrate that denosumab has beneficial effects on the measures of osteoporosis in Korean postmenopausal women.     

Farnesyl diphosphate synthase: a novel genotype association with bone mineral density in elderly women

OBJECTIVE: We evaluated the association between a single nucleotide polymorphism in the farnesyl diphosphate synthase gene (FDPS), BMD and bone turnover markers. METHODS: Two hundred and eighty-three community-dwelling Caucasian women aged 65 or older were screened from the greater Boston area. A validated FDPS SNP (rs2297480, A/C) was genotyped and evaluated for effect on bone mineral density (spine, hip, forearm) and bone turnover markers (urine N-telopeptide cross-linked collagen type 1, osteocalcin and bone-specific alkaline phosphatase). RESULTS: BMD was lower at all sites measured in women with the C/C or C/A genotypes. Statistically significant differences (p<0.05) were found at the PA spine, trochanter, distal radius, and proximal ulna after adjustment for age and BMI. No significant differences were found in bone turnover markers. CONCLUSION: These findings suggest that a single nucleotide polymorphism in the FDPS gene (rs2297480) may be a genetic marker for lower BMD in postmenopausal Caucasian women.     

The effect of soy protein isolate on bone metabolism

OBJECTIVE: This double-blind, 15-month pilot study was designed to investigate the effect of soy protein isolate with varying concentrations of isoflavones on early postmenopausal bone loss and lipids. DESIGN: A total of 65 women, with a mean age of 55 years and 7.5 years since menopause, were randomized to one of three groups; soy protein with 96 mg isoflavones/day, soy with 52 mg isoflavones/day, or soy without isoflavones (< 4 mg isoflavones/day). Soy was given for 9 months and then discontinued; participants were followed for an additional 6 months. Bone mineral density (BMD) and blood lipids were measured during this time. RESULTS: Measurement of serum isoflavones at 3 months showed dose-related increases in the three groups. There was no significant effect of the soy supplements on BMD of the spine or femoral neck in any of the three groups. BMD increased significantly in the trochanter at 9 months (P = 0.0219) and at 15 months (P < 0.05) in the group given isoflavone-free soy compared with the other two groups. There was no significant effect of soy on lipid metabolism at the end of the intervention. CONCLUSION: The present study did not find a significant positive effect of soy protein isolate supplemented with isoflavones on BMD and the serum lipid profile in early postmenopausal women.     

Marked Individual Variation in Isoflavone Metabolism After a Soy Challenge Can Modulate the Skeletal Effect of Isoflavones in Premenopausal Women

Soy-isoflavones may act as estrogenic agonists or antagonists depending on the endogenous hormone status. These clinical effects can be exerted variably in individuals by the metabolic ability to produce a more potent metabolite than precursors. The objective of this randomized, double-blind, placebo-controlled study was to investigate the skeletal effect of isoflavones according to their metabolic variability in premenopausal women. Volunteers were randomly assigned to receive either soy-extract isoflavones (n=32) or lactose (n=21) once a day for three menstrual cycles. After intervention, the urinary excretions of isoflavones and their metabolites were significantly higher in the soy group than in the placebo group and showed a large inter-individual variation. Women in the soy group were divided into subgroups according to their ability to excrete more potent metabolites. Serum osteocalcin and urine deoxypyridinoline showed a tendency to increase after a challenge in equol high-excretors. Serum osteocalcin concentration in the genistein high-excretors increased significantly after a challenge (P=0.04) but did not increase in either the placebo or genistein low-excretors. An estrogenic antagonistic effect of isoflavones on bone turnover was observed in premenopausal women who are able to produce more potent metabolites.     

Changes in bone markers after once-weekly low-dose alendronate in postmenopausal women with moderate bone loss

BACKGROUND: High bone turnover, with bone resorption exceeding bone formation, is a major mechanism of postmenopausal osteoporosis. Therefore, inhibition of bone resorption is a rational approach for the prevention of bone loss. The objective of the current study was to determine the short-term efficacy of once-weekly low-dose alendronate in the prevention of bone loss, via bone turnover markers, in early postmenopausal Korean women with moderate bone loss. METHODS: This study involved a 12-week, randomized, double-blind clinical trial that compared the effects of placebo with alendronate 20mg once weekly. All subjects received supplemental calcium 600 mg and vitamin D 400IU daily. We recruited 63 postmenopausal women (ranging from 50 to 65 years of age) with the lowest lumbar spine bone mineral density (BMD) at least 2.0 S.D. below the mean value for young healthy adults. BMD was measured at baseline and serum alkaline phosphatase (ALP), osteocalcin, C-terminal telopeptide of type I collagen (CTX), and osteoprotegerin (OPG) were measured at baseline and 12 weeks after treatment. RESULTS: We randomly assigned 63 women to either placebo or alencronate 20 mg once a week for 3 months. Forty-nine women continued and completed all 3 months. After 3 months, bone resorption markers were significantly decreased in the alendronate group than in the placebo group: CTX -47.2% vs. 15% (p<0.01), ALP 1.6% vs. 25.9% (p=0.01), osteocalcin -29.2% vs. -13.6 (p=0.06). Women who received alendronate showed similar results to those who received placebo with regard to adverse events. CONCLUSION: Once-weekly low-dose alendronate may be a cost-effective and safe method of suppressing bone turnover in early postmenopausal women with moderate bone loss.     

Relationship of osteocalcin and matrix Gla protein gene polymorphisms to serum osteocalcin levels and bone mineral density in postmenopausal Korean women

OBJECTIVE: To investigate the relationship of osteocalcin and matrix Gla protein (MGP) gene polymorphisms to serum osteocalcin levels, and bone mineral density (BMD) in postmenopausal Korean women. DESIGN: The osteocalcin gene Hind III and MGP gene cytosine-adenine polymorphisms were analyzed in 267 postmenopausal Korean women. Serum osteocalcin, bone alkaline phosphatase, C-telopeptide of type I collagen, and BMD at the lumbar spine and femoral neck were measured. RESULTS: No significant differences in BMD of the lumbar spine and femoral neck were observed across MGP genotypes, whereas a significant lower BMD at the lumbar spine (but not at the femoral neck) was observed in women with the (h) allele (lower case 'h' signifies the presence of the Hind III site) in a dose-response manner. Serum osteocalcin levels among bone turnover markers studied were significantly higher in women without the 210-bp MGP (cytosine-adenine) allele, or with the osteocalcin hh genotype. CONCLUSIONS: The osteocalcin gene Hind III polymorphism is a genetic factor that is associated with BMD of the lumbar spine in Korean women, and Gla gene polymorphisms are associated with higher osteocalcin levels.     

骨代谢相关基因多态性与盐酸雷洛昔芬对绝经后骨质疏松妇女骨密度和骨转换指标影响的关系

目的了解骨代谢相关基因多态性与盐酸雷洛昔芬( raloxifene,RLX)对绝经后骨质疏松妇女骨密度(bone mineral density, BMD)和骨转换指标影响的关系.方法为随机、对照和双盲试验,入选47～74岁68例无亲缘关系的绝经后骨质疏松汉族妇女,随机分为RLX组和安慰剂组(各34例),RLX组日服RLX 60 mg,安慰剂组服与RLX外观一致的安慰剂,共1年.在服药前、服药后6月和12月时,检测BMD和骨转换指标包括血清1型胶原羧基末端肽(C-telopeptide, CTX)和骨钙素(osteocalcin, BGP).分析雌激素受体1基因(estrogen receptor 1 gene,ESR1)Xba Ⅰ和PvuⅡ位点、ESR2基因RasⅠ位点、维生素D受体基因(vitamin D receptor, VDR)FokⅠ和CDX2结合位点的多态性. 结果共58例完成整个试验,研究结束时RLX组腰椎2～4(L2～4)、全髋部和大转子BMD增加的百分数,以及血清CTX和BGP水平下降的百分数与安慰剂组比较差异均有统计学意义(P<0.05或P<0.01).治疗后12个月,RLX组VDR FokⅠ FF基因型者(n=8)全髋部和大转子BMD值平均下降各为1.98%±4.86%和2.26%±4.73%,而Ff/ff基因型者(n=21)平均增加各为2.52%±2.75%和2.74%±2.97%(P<0.05);ESR1 PvuⅡ位点PP/Pp基因型者(n=17)全髋部BMD明显增加(2.12%±2.78%),而pp基因型者(n=12)呈下降(-1.34%±3.73%)(P<0.05).但上述5个位点多态性与安慰剂组各指标变化均无相关性. 结论 RLX对绝经后骨质疏松妇女BMD的作用受VDR基因FokⅠ和ESR1基因PvuⅡ多态性的调节.在临床选择该药物时,可根据应用对象的基因型做有益决策之用.     

Effect of raloxifene and clodronate on bone density in postmenopausal osteoporotic women

The aim of the present study was to determine the safety and efficacy of combined therapy with raloxifene (RLX) and clodronate (CLD) in postmenopausal women. We enrolled 45 women with postmenopausal osteoporosis. The patients were randomly assigned to two different therapeutic groups: RLX 60 mg/day (n = 23) and RLX 60 mg/day plus CLD 100 mg intramuscularly (i.m.) once every 10 days (n = 22); 1 g of calcium and 800 IU of vitamin D3 were also given daily to both groups. Lumbar and femoral bone mineral density (BMD) were assessed at baseline and after 12 months of therapy using the dual X-ray absorptiometry technique (Norland XR36). We measured the bone turnover markers NTx and CTx, bone alkaline phosphatase (BAP) and osteocalcin at baseline and after 12 months of therapy. Our data demonstrate that 1 year of combined RLX+CLD therapy induced a higher increase in lumbar BMD than treatment with RLX alone as well as a major decrease in bone resorption markers, suggesting an additive effect of CLD on bone mass and inhibition of bone turnover. Furthermore, after 1 year of therapy levels of bone formation markers (osteocalcin and BAP) had increased in both groups, but the increase in osteocalcin and BAP was significantly higher in the RLX+CLD treated group, suggesting that, in addition to its inhibitory effects on resorption, CLD might also have stimulatory effects on mature osteoblast activity.     

Non-association Between Polymorphisms of the Frizzled Receptor Genes and Bone Mineral Density in Postmenopausal Korean Women

We investigated the association between single nucleotide polymorphisms (SNPs) in the frizzled (FZD) genes in the Wnt signal pathway and circulating osteoprotegerin (OPG), soluble receptor activator of NF-κB ligand (sRANKL) levels, bone turnover markers, and bone mineral density (BMD) in postmenopausal women. The SNPs in the FZD1, FZD5, FZD6, FZD7, and FZD9 genes were analyzed by direct sequencing in 371 postmenopausal Korean women. Levels of serum OPG, sRANKL, osteocalcin, C-telopeptide of type I collagen, calcium, parathyroid hormone and calcitonin, and BMD at the lumbar spine and femoral neck were measured. The SNPs in the FZD1, FZD5, FZD7, and FZD9 genes, and in exon 2 of the FZD6 gene were not observed. No significant differences in the adjusted BMD of lumbar spine and femoral neck and serum levels of OPG, sRANKL, and bone markers were noted among the single or haplotype genotypes of the L345M and E664A SNPs in the FZD6 gene and the distributions of these single or haplotype genotypes were not different according to the bone mass status. In conclusion, the polymorphisms of the FZD genes are not associated with BMD of the lumbar spine and femoral neck, bone turnover markers, or circulating OPG-sRANKL in Korean women.     

The effects of fructo-oligosaccharides in combination with soy protein on bone in osteopenic ovariectomized rats

OBJECTIVE: The intestinal microflora is important in rendering soy isoflavones bioavailable by facilitating their conversion to equol. Hence, substances that can modulate the intestinal microflora could affect the bioavailability of isoflavones. In this study, we examined the effects of fructo-oligosaccharides (FOS), a prebiotic, on enhancing the effects of soy isoflavones on bone in ovariectomized osteopenic female rats. DESIGN: Sixty-three 9-month-old female Sprague-Dawley rats were either sham-operated (Sham; one group) or ovariectomized (Ovx; four groups) and were fed a control diet for 3 months to induce bone loss. After bone loss was confirmed via dual-energy x-ray absorptiometry, rats were placed on dietary treatment for 4 months. The Sham and one Ovx group received a control diet, and the remaining Ovx groups received either a soy protein-based diet (Soy), a FOS-supplemented diet (FOS), or a soy protein-based and FOS-supplemented diet (Soy+FOS). Before the termination of the study, whole-body bone mineral density (BMD) and bone mineral content (BMC) were assessed under anesthesia. Immediately after euthanasia, bone specimens were collected for the assessments of BMD, BMC, and biomechanical and microarchitectural properties. RESULTS: Whole-body BMD values were significantly higher in FOS and Soy+FOS groups compared with Ovx controls. The tibial BMC increased by 10%, 6%, and 4% in Soy, FOS, and Soy+FOS groups, respectively, compared to the Ovx control group. FOS and FOS+Soy treatments had the most pronounced effects in enhancing lumbar BMC and BMD. The FOS+Soy combination effectively improved tibial microarchitectural properties by enhancing trabecular number and lowering trabecular separation compared with Ovx controls. The effects of dietary treatments on lumbar microarchitectural properties were minimal and biomechanical properties of the femur were not affected by any of the dietary treatments. CONCLUSION: Our findings suggest that, although incorporation of either soy or FOS in the diet of Ovx rats can improve BMD of the whole body, tibiae, and lumbar vertebrae, their combination had no any additive effects. However, in terms of microarchitecture, the combination of soy and FOS had a greater effect in reversing the loss of certain microarchitectural parameters such as tibial trabecular number, separation, and thickness.     

Postmenopausal osteoporosis and alendronate

Osteoporosis is a systemic metabolic disorder associated with a decreased bone mass and resistance. Bisphosphonates suppress bone resorption and bone turnover by a mechanism that depends on their structure. They are characterized by low gastrointestinal absorption. In postmenopausal women, alendronate (ALN) reduces bone resorption markers and increases bone mineral density (BMD) in the lumbar spine, femoral neck, and total body. Individuals receiving ALN have been studied for up to 10 years with an apparent linear increase in BMD over that time period estimated at 13.7% at the lumbar spine. Treatment with ALN reduced the risk of both vertebral and non-vertebral fractures, including hip fractures, in postmenopausal women with osteoporosis. Direct comparisons of the results obtained with different antiresortive agents is difficult, because the designs of the respective studies, populations and other factors. However, the meta-analysis of available publications seems to indicate that ALN reduces the relative risk of vertebral fractures in a greater proportion than any other agent. Furthermore, ALN prevents the reduction in BMD after hormone replacement therapy discontinuation.     

Oral hormone therapy with 17beta-estradiol and 17beta-estradiol in combination with norethindrone acetate in the prevention of bone loss in early postmenopausal women: dose-dependent effects

OBJECTIVE: A 2-year multicenter, double-blind, randomized, placebo-controlled study examined the efficacy and safety of different doses of 17beta-estradiol (E(2)) alone and continuous-combined oral formulations of E(2) and norethindrone acetate (NETA) versus placebo in the prevention of bone loss in newly menopausal women. DESIGN: Patients were randomized to one of seven groups: placebo, E(2) 0.25 mg, E2 0.5 mg, E(2) 1 mg, E(2) 1 mg/NETA 0.25 mg, E(2) 1 mg/NETA 0.5 mg, or E(2) 2 mg/NETA 1 mg. Treatment was a once-daily tablet taken for 26 months. The primary efficacy endpoint was the change in bone mineral density (BMD) at the lumbar spine, measured by dual-energy x-ray absorptiometry, at screening and at 13, 19, and 26 months. BMD changes at the femoral neck and trochanter were also assessed. Biochemical markers of bone metabolism were measured at baseline, and at 3, 6, 13, 19, and 26 months. Histological diagnoses of endometrial samples were tabulated for each treatment group. RESULTS: A total of 327 women were randomized and 189 women completed the 2-year trial. BMD at the lumbar spine decreased 2.3% in the placebo group. The lowest dose of unopposed E(2) prevented bone loss at the spine and hip. Significant increases in spine BMD compared with placebo occurred in all groups of treatment with E(2) and were more pronounced in the combination groups. Compared with placebo, women receiving active treatment experienced greater reductions in bone resorption markers. The effects were evident by 6 months and generally remained stable thereafter. Adverse events, primarily associated with the endometrium, were the most common reasons for discontinuation. CONCLUSIONS: There is a dose-dependent effect of E(2) on BMD. The addition of NETA seems to enhance the response in BMD observed with E(2). Low doses of E(2) (1 mg and lower) can be considered for the prevention of osteoporosis, while titrating the hormone dose to individual patient's needs.     

Medroxyprogesterone acetate with Zoladex for long-term treatment of fibroids: effects on bone density and patient acceptability

A randomized trial was carried out to investigate the effect of 12 months administration of the gonadotrophin-releasing hormone agonist (GnRHa) Zoladex in combination with either placebo or medroxyprogesterone acetate (MPA) from the third month. Bone density, markers of bone resorption, symptoms and uterine volume were monitored in 24 women with symptomatic fibroids or menstrual problems. A total of 21 women were recruited to act as controls for the assessment of bone parameters. Vasomotor side-effects were reduced significantly in the MPA-treated group. The reduction in uterine volume in women with fibroids was not impaired by the addition of MPA. The bone markers osteocalcin and alkaline phosphatase were assessed in plasma, and the cross-links pyridinoline and deoxypyridinoline measured in urine. Changes in these markers are reported which suggest increases in bone resorption during the period of observation. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry at the spine and forearm. The net reduction in BMD at the spine in the treated groups was 4.30 +/- 0.59% at 6 months and 7.50 +/- 0.78% at 1 year, with no change in the control group. No change was seen in forearm BMD. No protective effect was observed when MPA was added. At 1 year after the completion of treatment, BMD remained significantly below baseline, and this has implications for the prolonged use of GnRHa.      

Effects of nandrolone decanoate on bone mass in established osteoporosis

A double-blind, randomized, placebo-controlled study was conducted in 46 postmenopausal women with established osteoporosis in order to assess the long-term effects of nandrolone decanoate on the bone mineral density (BMD) of the lumbar vertebrae and of the distal third of the radius and on the biochemical markers of bone turnover. The patients received intramuscular injections of placebo or 50 mg nandrolone decanoate every 3 weeks for 18 months. Thirty-two of the initial 46 patients completed 1 year of study and 25 completed the whole study period of 18 months. Overall, vertebral BMD increased by 2.9% in the nandrolone decanoate group and fell by 2.3% in the placebo group. Radial BMD showed a slight but transient improvement, with a subsequent return to basal levels in the nandrolone decanoate group, whereas there was a progressive decrease in the placebo group. Patients treated with nandrolone decanoate also complained less of bone pain. Urinary hydroxyproline decreased significantly in treated patients, whereas osteocalcin tended to increase, but the change was not significant. HDL cholesterol concentrations decreased only slightly and haemoglobin increased significantly in the nandrolone decanoate group. Two patients treated with nandrolone decanoate withdrew from the study because of hirsutism and hoarseness. The results indicate that nandrolone decanoate exerts positive effects on vertebral BMD and on bone pain in patients with established postmenopausal osteoporosis.     

Soy protein and bone mineral density in older men and women: a randomized trial

OBJECTIVE: Test the hypothesis that soy isoflavone supplementation preserves bone mineral density (BMD) in men and women. METHODS: We conducted a controlled, parallel-arm, double-blinded trial with 145 participants, 50-80 years, with random assignment to soy beverage daily for 12 months. Active treatment (+ISO) received soy protein containing 83 mg isoflavones (45.6 mg genistein, 31.7 mg daidzein), aglycone units; the comparison group (-ISO) received soy protein containing 3mg isoflavones. We measured BMD using dual-energy X-ray absorptiometry at the total hip and posterior-anterior spine (L1-L4) at baseline in 22 women and 123 men, and at 12 months in 13 women and 98 men. We used linear mixed models to test for an isoflavone effect on percentage BMD change from baseline in spine and hip. RESULTS: Among all participants, mean percent change in spine BMD (+/-S.E.) was 0.16+/-0.44 in -ISO (P=0.10) at 12 months. Treatment effects on spine BMD were significantly greater in women than men (P=0.01). At 12 months, in women, mean percent change was 0.58+/-0.70 in +ISO and -1.84+/-0.86 in -ISO (P=0.05); among men it was 1.32+/-0.53 in +ISO and 0.31+/-0.48 in -ISO (P=0.16). By comparison, percent change in hip BMD was similar in the treatment groups, and was not different between men and women. Mean percent change in hip BMD from baseline to 12 months was 0.54+/-0.38 in +ISO and -0.13+/-0.36 in -ISO (P=0.20) among all participants. CONCLUSIONS: Soy protein containing isoflavones showed a modest benefit in preserving spine, but not hip BMD in older women.     

Changes in biochemical bone markers during pregnancy and puerperium

To elucidate the changes in bone turnover during pregnancy and puerperium, we measured serially the levels of serum osteocalcin and urine deoxypyridinoline (Dpy) as markers of bone formation and bone resorption, respectively, in 22 healthy women with normal pregnancy. Nineteen non-pregnant women served as control. The Dpy levels increased significantly at 16 weeks of pregnancy and remained elevated thereafter. The levels of osteocalcin, however, were significantly decreased at 16 weeks of pregnancy and elevated later at 6 weeks postpartum. Bone turnover ratio (Dpy/osteocalcin) continued to rise during pregnancy, but returned to control levels 6 weeks after delivery. Dpy levels and bone turnover ratio during puerperium tended to be higher in 17 breast-feeding women than those of 5 exclusive bottle-feeders. In conclusion, bone resorption begins to increase from the second trimester of pregnancy and calcium release from bone tissue might play a major role in calcium homeostasis during the whole period of pregnancy as well as during lactation.     

Once-weekly alendronate 70 mg and raloxifene 60 mg daily in the treatment of postmenopausal osteoporosis

OBJECTIVE: To compare the efficacy and tolerability of once-weekly (OW) alendronate (ALN) 70 mg and raloxifene (RLX) 60 mg daily in the treatment of postmenopausal osteoporosis. DESIGN: This 12-month, randomized, double-blind study enrolled 456 postmenopausal women with osteoporosis (223 ALN, 233 RLX) at 52 sites in the United States. Efficacy measurements included lumbar spine (LS), total hip, and trochanter bone mineral density (BMD) at 6 and 12 months, biochemical markers of bone turnover, and percent of women who maintained or gained BMD in response to treatment. The primary endpoint was percent change from baseline in LS BMD at 12 months. Adverse experiences were recorded to assess treatment safety and tolerability. RESULTS: Over 12 months, OW ALN produced a significantly greater increase in LS BMD (4.4%, P < 0.001) than RLX (1.9%). The percentage of women with > or = 0% increase in LS BMD (ALN, 94%; RLX, 75%; P < 0.001) and > or =3% increase in LS BMD (ALN, 66%; RLX, 38%; P < 0.001) were significantly greater with ALN than RLX. Total hip and trochanter BMD increases were also significantly greater (P < or =0.001) with ALN. Greater (P < 0.001) reductions in N-telopeptide of type I collagen and bone-specific alkaline phosphatase were achieved with ALN compared with RLX at 6 and 12 months. No significant differences in the incidence of upper gastrointestinal or vasomotor adverse experiences were seen. CONCLUSION: ALN 70 mg OW produced significantly greater increases in spine and hip BMD and greater reductions in markers of bone turnover than RLX over 12 months. A greater percentage of women maintained or gained BMD on ALN than RLX. Both medications had similar safety and tolerability profiles.     

Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg 17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with osteopenia [lumbar spine bone mineral density (BMD) between -1.0 and -2.5 SD of the premenopausal mean value] were enrolled in a 2-year prospective, randomized study, and 70% completed. Treatments were 1 mg 17beta-estradiol + 0.125 mg trimegestone (n = 179) or placebo (n = 181), given as daily oral therapy. All received a daily supplement of 500 mg calcium and 400 IU vitamin D. BMD measurements at the lumbar spine, total hip, and femoral neck as well as blood and urinary biochemical markers of bone turnover (serum osteocalcin), serum bone-specific alkaline phosphatase, serum CrossLaps, and urinary CrossLaps took place regularly. RESULTS: BMD increases relative to placebo were 6.3%, 3.9%, and 3.8% at the lumbar spine, total hip, and femoral neck, respectively (all P < 0.001). The biochemical markers of bone turnover were suppressed accordingly. Serum CrossLaps and urinary CrossLaps decreased rapidly, by 52% and 54%, respectively, whereas serum osteocalcin and serum bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy is efficient in increasing BMD in an osteopenic postmenopausal population. Furthermore, it is well tolerated, with few adverse events and an early bleeding control, which is likely to improve compliance to the treatment over the long term.     

Reduced bone mass detected by bone quantitative ultrasonometry and DEXA in pre- and postmenopausal women with endogenous subclinical hyperthyroidism

BACKGROUND: Although overt hyperthyroidism is a well known cause of bone loss, systemic effects of subclinical hyperthyroidism (SH) are still a matter of debate. Objective: The aim of this cross-sectional study was to evaluate the effect of endogenous SH on bone in relation to the menopausal status. METHODS: Bone mass and turnover were assessed in a group of 60 patients with endogenous SH due to multinodular goitre; 30 of them were premenopausal and 30 early postmenopausal (mean age, 40.9 +/- 7.3 and 57.7 +/- 6.75, respectively). Sixty healthy women matched for age-, BMI- and menopausal status served as controls. Three different skeletal sites were evaluated using two different techniques: lumbar spine and femoral neck were assessed by DEXA whereas the proximal phalanges were evaluated by quantitative ultrasonometry (QUS), measuring the amplitude-dependent speed of sound (Ad-SoS). Serum osteocalcin and urinary deoxypyridinoline (DPD) were also determined as markers of bone turnover. RESULTS: A significant decrease was found in femoral BMD (P < 0.05) and phalangeal Ad-SoS (P < 0.001) in pre- and postmenopausal patients compared to controls, being greater in those postmenopausal. Lumbar BMD was decreased only in postmenopausal patients (P < 0.05). Bone turnover markers were higher in patients than in controls and in post- than in the premenopausal ones. A significant negative correlation was found between femoral BMD, Ad-SoS and serum free T3 levels, the latter considered a marker of disease activity. CONCLUSIONS: A significant increase in bone turnover markers and a decrease in bone mass was found in women affected by endogenous SH, being greater in early postmenopausal patients. Cortical rich bone was mainly affected. Both QUS and the conventional DEXA technique were equally able to determine bone density decrease related to mild thyroid hormone excess and sexual hormone decrease.