Clinical Significance of 1-year Treatment with Raloxifene on Bone and Lipid Metabolism in Japanese Postmenopausal Women with Osteoporosis

Majima, T.; Komatsu, Yasato; Shimatsu, Akira; Satoh, Noriko; Fukao, Akira; Ninomiya, Kiyoshi; Matsumura, Tadashi; Nakao, Kazuwa

doi:10.1507/endocrj.k06-208

Cited by 7 publications

(14 citation statements)

References 35 publications

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“…Lipid-lowering drugs (statins) increase the BMD of the hip or femoral neck [10][11][12][13] . However, some anti-osteoporotic drugs such as selective estrogen receptor modulators (SERMS, eg raloxifene) only moderately reduce serum levels of TC and LDL-C [14][15][16] . All of this evidence points to a clinical correlation between hyperlipidaemia and postmenopausal osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

Sheng

Tang

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the effects of high cholesterol diet on the development of osteoporosis and the underlying mechanisms in rats. Methods: Female Sprague-Dawley rats were randomly separated into 3 groups: (1) the high cholesterol fed rats were fed a high cholesterol diet containing 77% normal diet food, 3% cholesterol and 20% lard for 3 months; (2) ovariectomised (OVX) rats were bilaterally ovariectomised and fed a standard diet; and (3) the control rats were fed the standard diet. Bone mineral density (BMD) of the rats was measured using dual-energy X-ray absorptiometry. Serum levels of oestradiol (E2), osteocalcin (BGP) and carboxy-terminal collagen crosslinks (CTX) were measured using ELISA. Gene expression profile was determined with microarray. Mouse osteoblast cells (MC3T3-E1) were used for in vitro study. Proliferation, differentiation and oxidative stress of the osteoblasts were investigated using MTT, qRT-PCR and biochemical methods. Results: In high cholesterol fed rats, the femur BMD and serum BGP level were significantly reduced, while the CTX level was significantly increased. DNA microarray analysis showed that 2290 genes were down-regulated and 992 genes were up-regulated in this group of rats. Of these genes, 1626 were also down-regulated and 1466 were up-regulated in OVX rats. In total, 370 genes were up-regulated in both groups, and 976 genes were down-regulated. Some of the down-regulated genes were found to code for proteins involved in the transforming growth factor beta (TGF-β)/bone morphogenic protein (BMP) and Wnt signaling pathways. The up-regulated genes were found to code for IL-6 and Ager with bone-resorption functions. Treatment of MC3T3-E1 cells with cholesterol (12.5-50 μg/mL) inhibited the cell proliferation and differentiation in vitro in a concentration-dependent manner. The treatment also concentration-dependently reduced the expression of BMP2 and Cbfa1, and increased the oxidative injury in MC3T3-E1 cells. Conclusion:The results suggest a close correlation between hypercholesterolaemia and osteoporosis. High cholesterol diet increases the risk of osteoporosis, possible via inhibiting the differentiation and proliferation of osteoblasts.

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Section: Introductionmentioning

confidence: 99%

High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

Sheng

Tang

et al. 2011

Acta Pharmacol Sin

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“…Of the 15 publications included for review, there were seven randomized controlled trials29–35 reporting evidence for efficacy and eight observational studies24,36–42 reporting evidence of effectiveness (Table 1). Evidence of safety was reported in 1229–33,35–38,40–42 of the 15 publications.…”

Section: Resultsmentioning

confidence: 99%

“…Findings for BMD were reported in eleven of the 15 publications, and included BMD of the lumbar spine (nine publications),29,31–33,35–38,40 of the femoral neck, total hip, or total neck (six publications),29,32,33,36–38 or of other regions in the hip (five publications) 24,33,36,38,39. Findings were reported as the percentage change in BMD from baseline to 52 weeks or BMD at baseline and at 52 weeks in all publications.…”

Section: Resultsmentioning

confidence: 99%

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Systematic review of raloxifene in postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia)

Fujiwara¹,

Hamaya²,

Sato³

et al. 2014

CIA

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PurposeTo systematically review the literature describing the efficacy, effectiveness, and safety of raloxifene for postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia).Materials and methodsMedline via PubMed and Embase was systematically searched using prespecified terms. Retrieved publications were screened and included if they described randomized controlled trials or observational studies of postmenopausal Japanese women with osteoporosis or osteopenia treated with raloxifene and reported one or more outcome measures (change in bone mineral density [BMD]; fracture incidence; change in bone-turnover markers, hip structural geometry, or blood–lipid profile; occurrence of adverse events; and change in quality of life or pain). Excluded publications were case studies, editorials, letters to the editor, narrative reviews, or publications from non-peer-reviewed journals; multidrug, multicountry, or multidisease studies with no drug-, country-, or disease-level analysis; or studies of participants on dialysis.ResultsOf the 292 publications retrieved, 15 publications (seven randomized controlled trials, eight observational studies) were included for review. Overall findings were statistically significant increases in BMD of the lumbar spine (nine publications), but not the hip region (eight publications), a low incidence of vertebral fracture (three publications), decreases in markers of bone turnover (eleven publications), improved hip structural geometry (two publications), improved blood–lipid profiles (five publications), a low incidence of hot flushes, leg cramps, venous thromboembolism, and stroke (12 publications), and improved quality of life and pain relief (one publication).ConclusionFindings support raloxifene for reducing vertebral fracture risk by improving BMD and reducing bone turnover in postmenopausal Japanese women with osteoporosis or osteopenia. Careful consideration of fracture risk and the risk–benefit profile of antiosteoporosis medications is required when managing patients with osteoporosis.

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“…These subjects include a part of those in another recent study of ours [19], and are a part of those in another one [20]. The diagnosis of osteoporosis was established on the basis of T-score of bone mineral density (BMD) at least 2.5 SDs below the young adult mean, and along with the criteria for the diagnosis of osteoporosis in Japan [21].…”

Section: Subjectsmentioning

confidence: 99%

Association between Baseline Values of Bone Turnover Markers and Bone Mineral Density and Their Response to Raloxifene Treatment in Japanese Postmenopausal Women with Osteoporosis

et al. 2008

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Abstract. It has been well established that raloxifene improves bone turnover, increases bone mineral density (BMD), and reduces the risk of fractures. However, it remains obscure which patients are more likely to respond to treatment with raloxifene in patients with postmenopausal osteoporosis. The purpose of this study was to investigate associations between baseline values of BMD and bone turnover markers (BTMs) and changes of those values after 1-year treatment with raloxifene. Sixty-eight Japanese postmenopausal women with untreated osteoporosis were selected for this study, among whom 58 patients (mean age 70.40 ± 9.2 years) completed this study. Lower baseline values of BMD at the lumbar spine, the femoral neck, and the distal radius were significantly correlated with greater increases of BMD at those corresponding sites after 1-year treatment with raloxifene. On the other hand, higher baseline values of bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx) were significantly correlated with greater reductions of BAP and NTx, respectively, after 1-year treatment with raloxifene. Although longer and larger studies with fracture endpoints are needed, our findings suggest that baseline values of BMD and BTMs can be used to predict subsequent skeletal response to raloxifene therapy in Japanese postmenopausal women with osteoporosis.

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Clinical Significance of 1-year Treatment with Raloxifene on Bone and Lipid Metabolism in Japanese Postmenopausal Women with Osteoporosis

Cited by 7 publications

References 35 publications

High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

Systematic review of raloxifene in postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia)

Association between Baseline Values of Bone Turnover Markers and Bone Mineral Density and Their Response to Raloxifene Treatment in Japanese Postmenopausal Women with Osteoporosis

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