Blueberry prevents bone loss in ovariectomized rat model of postmenopausal osteoporosis

The objective of the present study was to explore the bone protective role of blueberry in an ovariectomized rat model. Thirty 6-month-old female Sprague-Dawley rats were either sham-operated (Sham) or ovariectomized (Ovx) and divided into three groups: Sham, Ovx (control), Ovx+blueberry (5% blueberry w/w). After 100 days of treatment, rats were euthanized, and blood and tissues were collected. Bone mineral density (BMD) and content of whole body, right tibia, right femur and fourth lumbar vertebra were assessed via dual-energy X-ray absorptiometry. As expected, Ovx resulted in loss of whole-body, tibial, femoral, and 4th lumbar BMD by approximately 6%. Blueberry treatment was able to prevent the loss of whole-body BMD and had an intermediary effect on prevention of tibial and femoral BMD when compared to either Sham or Ovx controls. The bone-protective effects of blueberry may be due to suppression of Ovx-induced increase in bone turnover, as evident by lowered femoral mRNA levels of alkaline phosphatase, collagen type I and tartrate-resistant acid phosphatase to the Sham levels. Similarly, serum osteocalcein levels were also lower in the blueberry group when compared to the Ovx control group, albeit not significantly. In summary, our findings indicate that blueberry can prevent bone loss as seen by the increases in BMD and favorable changes in biomarkers of bone metabolism.     

Dietary intake of calcium and postmenopausal bone loss.

The use of calcium supplements to prevent postmenopausal bone loss and hence osteoporosis is widespread, but the evidence for their efficacy, either alone or in combination with other treatments, is contradictory. Skeletal measurements and dietary intake of calcium were determined in 59 healthy postmenopausal women, most of whom were within five years of the menopause. No correlation was found between current intake of calcium and either total calcium in the body or the density of trabecular or cortical bone in the forearm or vertebral trabecular bone. Dietary intake of calcium did not influence the rate of postmenopausal bone loss in the 54 women who completed 12 months of active or placebo treatment. Even when extremes of calcium intake were examined no difference was found in bone measurements between the women with the highest and lowest intakes. The results of this study suggest that the bone density of women in the early menopause is not influenced by current dietary intake of calcium.     

益生菌补充剂治疗绝经后骨质疏松症或骨量减少的系统评价

系统评价益生菌补充剂对绝经后骨质疏松症（PMOP）或骨量减少的有效性及安全性。

选取8个公共数据库,检索自建库至2022年9月,无语言限制,使用随机对照方法,评估补充益生菌补充剂对腰椎、股骨颈、总髋关节骨密度（BMD)、T值（T-value）、胶原降解产物（CTX）、I型前胶原氨基端前肽（PINP）、骨碱性磷酸酶（BALP）、骨钙素（BGP）水平和不良反应率的影响。

纳入了8篇RCT文献,647名参与者,治疗组有325名,对照组322名。结果显示益生菌组在提高PMOP和绝经后骨量减少患者的腰椎BMD、股骨颈BMD、T值、BGP和降低绝经后妇女CTX、BALP等方面显著优于对照组（P＜0.05）。亚组分析结果显示益生菌治疗PMOP患者后显著提高腰椎BMD、股骨颈BMD、全髋关节BMD、T值和降低CTX、BALP优于对照组（P＜0.05）。

益生菌干预PMOP和骨量减少患者后显著提高骨密度及降低骨代谢,对PMOP患者的作用更显著。

     

The relationship between bone marrow adipose tissue and bone metabolism in postmenopausal osteoporosis

Postmenopausal osteoporosis (PMOP) is a prevalent skeletal disorder associated with menopause-related estrogen withdrawal. PMOP is characterized by low bone mass, deterioration of the skeletal microarchitecture, and subsequent increased susceptibility to fragility fractures, thus contributing to disability and mortality. Accumulating evidence indicates that abnormal expansion of marrow adipose tissue (MAT) plays a crucial role in the onset and progression of PMOP, in part because both bone marrow adipocytes and osteoblasts share a common ancestor lineage. The cohabitation of MAT adipocytes, mesenchymal stromal cells, hematopoietic cells, osteoblasts and osteoclasts in the bone marrow creates a microenvironment that permits adipocytes to act directly on other cell types in the marrow. Furthermore, MAT, which is recognized as an endocrine organ, regulates bone remodeling through the secretion of adipokines and cytokines. Although an enhanced MAT volume is linked to low bone mass and fractures in PMOP, the detailed interactions between MAT and bone metabolism remain largely unknown. In this review, we examine the possible mechanisms of MAT expansion under estrogen withdrawal and further summarize emerging findings regarding the pathological roles of MAT in bone remodeling. We also discuss the current therapies targeting MAT in osteoporosis. A comprehensive understanding of the relationship between MAT expansion and bone metabolism in estrogen deficiency conditions will provide new insights into potential therapeutic targets for PMOP.     

Effect of salcatonin given intranasally on bone mass and fracture rates in established osteoporosis: a dose-response study.

OBJECTIVE--To study the dose related response of salmon calcitonin (salcatonin) given intranasally on bone mass and bone turnover and the effect of salcatonin on rates of fracture in elderly women with moderate osteoporosis. DESIGN--Double blind, placebo controlled, randomised group comparison. SETTING--Outpatient clinic for research into osteoporosis. SUBJECTS--208 healthy women aged 68-72 years who had a bone mineral content of the distal forearm on average 30% below the mean value for healthy premenopausal women. INTERVENTIONS--The 208 women were allocated randomly in blocks of four to two years of treatment with either salcatonin 50 IU, 100 IU, or 200 IU given intranasally or placebo. All groups received a calcium supplement of 500 mg. 32 of the women left the study before its end and 164 women complied with the study criteria throughout. MAIN OUTCOME MEASURES--Bone mineral content of the distal forearm and lumbar spine and rates of vertebral and peripheral fractures after two years of treatment. RESULTS--The average changes in bone mineral content of the spine showed positive outcomes of 1% (95% confidence interval -0.1% to 1.5%) in the group treated with calcium (placebo) and 3% (1.8% to 4.2%) in the group treated with salcatonin 200 IU. There was a significant dose related response to salcatonin, manifested by an increase of 1.0%/100 IU (0.2% to 1.7%, p = 0.008). The rate of patients with new fractures was reduced significantly in the women treated with salcatonin to about one third of that in the non-salcatonin treated women (relative risk 0.23 (0.07 to 0.77)). CONCLUSION--The results suggest that, compared with calcium alone, salcatonin given intranasally reduces the rates of fracture by two thirds in elderly women with moderate osteoporosis. Furthermore, it increases spinal bone mass in a dose dependent manner.     

Effect of salcatonin given intranasally on early postmenopausal bone loss.

OBJECTIVE--To study the effect of salmon calcitonin (salcatonin) given intranasally on calcium and bone metabolism in early postmenopausal women. DESIGN--Double blind, placebo controlled, randomised group comparison. SETTING--Outpatient clinic for research into osteoporosis. SUBJECTS--52 Healthy women who had had a natural menopause two and a half to five years previously. INTERVENTIONS--The 52 women were allocated randomly to two years of treatment with either salcatonin 100IU given intranasally (n = 26) or placebo (n = 26). Both groups received a calcium supplement of 500 mg daily. Seven of the women receiving salcatonin and six of those receiving placebo left the study before its end. MAIN OUTCOME MEASURES--Bone mineral content in the spine, the total skeleton, and the forearms after two years of treatment. RESULTS--Bone mineral content in the spine was significantly higher in the women who had received salcatonin than in those who had received placebo both after one year and after two years of treatment. After one year the difference was 3.8% (95% confidence interval 0.0 to 7.6%) and after two years it was 8.2% (3.8 to 12.6%). In contrast, the bone mineral content in the distal and proximal forearms and in the total skeleton declined similarly in both groups by about 2% each year, and after two years of treatment the differences between the groups were not significant. Biochemical estimates of bone turnover were not affected by salcatonin. CONCLUSION--The results suggest that salcatonin given intranasally in the dose used prevents bone loss in the spine of early post menopausal women but does not affect the peripheral skeleton.     

A preventive approach of the postmenopausal bone loss

In countries where osteoporosis in the ageing process tends to be a major problem, this phenomenon is of particular interest. The consequences of the osteoporosis in an ageing population, especially in the coming decades could create serious problems for the health authorities. It would be very interesting to see that in an early stage i.e. at menopause it could be influenced by prophylactic treatments. In a few countries the prophylactic approach of the menopausal osteoporosis has been already introduced. But it will take a long time before prophylaxis of postmenopausal osteoporosis could be considered as a standard and routine procedure.     

Reversal of postmenopausal vertebral bone loss by oestrogen and progestogen: a double blind placebo controlled study

Because of uncertainty about the place of hormones in the treatment of postmenopausal bone loss vertebral and forearm bone loss was measured by absorptiometry in early post-menopausal women before and after continuous or sequential treatment with combined oestrogen and progestogen in a double blind placebo controlled trial. Treatment with hormones significantly reversed the vertebral bone loss. The net gain in vertebral bone density amounted to 6·4% a year with continuous supplementation and 5·4% a year with sequential supplementation; the net gain in forearm bone density was lower (3·6% with continuous and 3·7% with sequential supplementation).Before a policy of supplementation with hormones can be recommended to all postmenopausal women with the aim of reducing the incidence of vertebral crush fractures further studies with different doses and combinations of hormones, administered over several years, are needed.     

Progressive loss of bone in the femoral neck in elderly people: longitudinal findings from the Dubbo osteoporosis epidemiology study.

OBJECTIVES--To determine prospectively the rates of change in bone mineral density in elderly people and to examine the relation between lifestyle and demographic factors and these rates of change. DESIGN--Longitudinal population based study. SETTING--Dubbo, New South Wales, Australia. SUBJECTS--Representative sample (n = 769) of residents aged > or = 60 on 1 January 1989. MAIN OUTCOME MEASURE--Rates of change in bone mineral density measured prospectively (mean scan interval 2.5 years) at the femoral neck and lumbar spine by dual energy x ray absorptiometry. RESULTS--Summary rates of loss in the femoral neck were 0.96% per year (95% confidence interval 0.64% to 1.28%) in women and 0.82% per year (0.52% to 1.12%) in men. Importantly, rates of loss at the femoral neck (both percentage and absolute) increased in both sexes with advancing age. No significant loss was evident in either sex at the lumbar spine, probably because of coexistent osteoarthritis. Lifestyle factors had only modest effects on rates of loss at either site. CONCLUSIONS--These data show that bone density of the femoral neck declines at an increasing rate in elderly people, and as this site is predictive of fracture suggest that treatment to minimise bone loss may be important even in very elderly people.     

Normal acquisition and loss of bone mass

The natural patterns of bone mass accumulation and loss with age represent the templates of individual life cycle periods that are distinguished by marked, physiologically and genetically identifiable, changes in bone mass. During the third trimester of pregnancy, maternal calcium absorption increases and the fetus accumulates about two-thirds of the total bone mass of the term infant. In early infancy, human milk calcium is derived primarily from maternal bone stores, which incur substantial bone losses that are quickly replenished during and after weaning. At puberty, a marked increase in bone mass occurs in conjunction with the initial physical and hormonal changes that characterize this stage. Calcium absorption and bone calcium deposition rates peak in females shortly before menarche. At that time, the bone calcium deposition rate is approximately five times that of adulthood. Skeletal bone mass reaches over 90% of its maximum by age 18 (earlier in females) but does not peak until age 25-30. At some point in mid-life, women experience perimenopause, the 3- to 5-year period prior to menopause during which estrogen levels begin to drop and there are marked increases in bone resorption and loss. Throughout adulthood, calcium absorption efficiency from the diet gradually declines.     

Role of the vitamin D-endocrine system in the pathophysiology of postmenopausal osteoporosis

Impaired calcium absorption and impaired adaptation to a low calcium diet are common features of aging in women and these processes are even more severely impaired in patients with osteoporotic fractures. The calcium absorption defects are associated with several abnormalities of the vitamin D-endocrine system including secondary hyperparathyroidism, intestinal resistance to 1,25-dihydroxyvitamin D (1,25(OH)(2)D) action, decreased 1,25(OH)(2)D production due to impaired 25(OH)D 1alpha-hydroxylase activity, and, in some elderly persons, nutritional deficiency of vitamin D. However, in postmenopausal women, most of these abnormalities are normalized by administration of physiologic replacement dosages of estrogen and, thus, appear to be secondary consequences of estrogen deficiency. Nonetheless, a minority of them, especially nutritional vitamin D deficiency and impaired 25(OH)D 1alpha-hydroxylase activity late in life, appear to be primary and are independent of estrogen deficiency.     

Treatment of spinal osteoporosis in postmenopausal women.

Ninety-five postmenopausal women with unequivocably wedged or compressed vertebrae in whom the recognised causes of secondary osteoporosis had been excluded were studied, 41 having no treatment and the rest one or more of six different treatments. The treatment regimens comprised calcium supplements, vitamin D, calcium and vitamin D, ethinyloestradiol or--where oestrogens were contraindicated--norethisterone, 1 alpha-hydroxycholecalciferol (1 alpha-OHD3), or hormones with 1 alpha-OHD3. The seven groups were reasonably comparable in most respects except that the hormone-treated patients were younger and had a higher initial cortical area ratio than the others, and the calcium- and hormone-treated groups had the best initial radio-calcium absorption. The untreated osteoporotic patients lost cortical bone more rapidly than do normal postmenopausal women. Three treatments (calcium, hormones, and 1 alpha OHD3 plus hormones) appear to be useful in modifying the disease, and two treatments (vitamin D and 1 alpha-OHD3) useless or even harmful. Vitamin D and 1 alpha-OHD3 are more safely used in conjunction with oestrogens, which protect bone against resorption, than on their own.     

Effect of misoprostol on bone mineral density in women with postmenopausal osteoporosis

OBJECTIVE: To evaluate the effect of misoprostol on bone mineral density in postmenopausal women. MATERIALS AND METHODS: The study was performed in a randomized controlled prospective manner in 90 women with menopause at Süleymaniye Maternity and Women's Diseases Teaching and Research Hospital between January and December 2003. Cases were divided into three groups each consisting of 30 women who were in menopause for at least 1 year and had t-scores less than -1 by dual energy X-ray densitometry (DEXA). Group I was treated with misoprostol and calcium, Group II received tibolone and calcium and Group III was given calcium only and considered as control group. In all patients, bone mineral density in L1-L4 vertebrae, femur neck and Ward triangle were measured by DEXA and t and z scores were calculated. RESULTS: All groups were similar demographically. Bone mineral density in L1-L4 vertebrae, femur neck and Ward triangle in the group treated with misoprostol, increased by 5, 8.1 and 3.6%, respectively. In the tibolone group, bone mineral density in L1-L4 vertebrae, femur neck and Ward triangle increased by 8.3, 5.3 and 7.8%, respectively. There was not a significant difference in t and z-scores and bone mineral density measurements between misoprostol and tibolon groups. CONCLUSION: Misoprostol may be an alternative treatment for patients with osteopenia and osteoporosis who are not suitable for hormone replacement therapy.     

M1 macrophage-derived exosomes aggravate bone loss in postmenopausal osteoporosis via a microRNA-98/DUSP1/JNK axis

Macrophages (Mφs) are master regulators of the immune response and may serve as therapeutic targets in aging societies. This study aimed to determine the function of M1Mφ-exosomes (Exos) in the development of osteoporosis (OP) and the involvement of microRNA (miR)-98 and dual specificity phosphatase 1 (DUSP1). A murine model of OP was established using ovariectomies (OVX). Bone loss was observed in OVX-treated mice, as manifested by reduced bone mineral density and decreased number of bone trabecula. The bone loss was further aggravated by treatment with M1Mφ-Exos. Exos also suppressed osteogenic differentiation of MC3T3-E1 cells. miRNA microarray analysis revealed that the miR-98 level was notably upregulated in cells after Exo treatment, and DUSP1 was confirmed as a target of miR-98. Meanwhile, downregulation of miR-98 or upregulation of DUSP1 restored the osteogenic differentiation ability of MC3T3-E1 cells. In addition, upregulation of DUSP1 reduced bone loss in murine bone tissues and suppressed JNK phosphorylation. In summary, M1Mφ-derived exosomal miR-98 exacerbates bone loss and OP by downregulating DUSP1 and activating the JNK signaling pathway. miR-98 may therefore serve as a therapeutic target in OP management.     

Relation of common allelic variation at vitamin D receptor locus to bone mineral density and postmenopausal bone loss: cross sectional and longitudinal population study.

OBJECTIVE: To determine whether common allelic variation at the vitamin D receptor locus is related to bone mineral density and postmenopausal bone loss. DESIGN: Cross sectional and longitudinal population study. SETTING: Outpatient clinic in research centre. SUBJECTS: 599 healthy women aged 27 to 72 and 125 women with low bone mass aged 55-77 had bone mineral density measured once in the cross sectional study. 136 women aged 45-54 were followed up for 18 years in the longitudinal study. MAIN OUTCOME MEASURES: Bone mineral density measured at the lumbar spine, hip, and forearm and rate of bone loss at different times over 18 years in relation to vitamin D receptor genotype as defined by the endonucleases ApaI, EsmI, and TaqI. RESULTS: Vitamin D receptor genotype was not related to bone mineral density at any site. The maximum difference between homozygotes was 1.3% (P = 0.33, n = 723). Women with low bone mineral density had almost the same genotype frequencies as the women with normal bone mineral densities. Vitamin D receptor genotype was not related to early postmenopausal bone loss from age 51 to 53 (mean (SD) total loss at the lower forearm -3.6% (3.6%)), late postmenopausal bone loss from age 63 to 69 (at the hip-6.2% (8.7%)), or to long term postmenopausal loss from age 51 to 69 (at the lower forearm-24.5% (11.4%)). CONCLUSION: Common allelic variation at the vitamin D receptor locus as defined by the endonucleases ApaI, EsmI, and TaqI is related neither to bone mineral density nor to the rate of bone loss in healthy postmenopausal Danish women.