Retard Bone Loss Research Articles

The Ginsenoside Exhibits Antiosteoporosis Effects in Ketogenic-Diet-Induced Osteoporosis via Rebalancing Bone Turnover.

Ginsenoside is widely used in China for therapeutic and healthcare practice. Ginsenoside-Rb2 shows the antiosteoporosis effects in ovariectomized rodents. However, the protective effects on osteoporosis induced by ketogenic diet (KD) remain unknown. Therefore, this study aimed at evaluating the effects of ginsenoside-Rb2 on KD-induced osteoporosis. Thirty mice were randomly divided into three groups: sham, KD, and KD + Rb2. Bone microstructures, biomechanical properties, concentrations of serum bone alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase (TRACP), and protein expression of osteocalcin (OCN), peroxisome proliferation-activated receptor γ (PPAR-γ), cathepsin K, and TRAP were evaluated after a 12-week intervention. The results show that KD induced significant bone loss and biomechanical impairment. Ginsenoside-Rb2 attenuated significant bone loss and maintained biomechanics in cancellous bone. The bone volume fraction increased from 2.3 to 6.0% in the KD + Rb2 group than that in the KD group. Meanwhile, ginsenoside-Rb2 effectively maintained biomechanical strengths in cancellous bone, increased serum BALP and decreased TRACP, and upregulated OCN and downregulated TRAP, PPAR-γ, and cathepsin K in the KD mice. This study demonstrated that ginsenoside-Rb2 retards bone loss and maintains biomechanics with KD. The underlying mechanism might be that ginsenoside-Rb2 inhibits bone resorption process and induces osteogenic differentiation, providing evidence for ginsenoside as being an alternative option for osteoporosis induced by KD.

Melatonin restores osteoporosis-impaired osteogenic potential of bone marrow mesenchymal stem cells and alleviates bone loss through the HGF/PTEN/Wnt/β-catenin axis.

Background:Previous studies reported that melatonin exerts its effect on mesenchymal stem cell (MSC) survival and differentiation into osteogenic and adipogenic lineage. In the current study we aimed to explore the effect of melatonin on osteoporosis and relevant mechanisms.Methods:Real-time qualitative polymerase chain reaction (RT-qPCR) and Western blot analysis were conducted to determine expression of HGF, PTEN, and osteoblast differentiation-related genes in ovariectomy (OVX)-induced osteoporosis mice and the isolated bone marrow MSCs (BMSCs). Pre-conditioning with melatonin (1 μmol/l, 10 μmol/l and 100 μmol/l) was carried out in OVX mice BMSCs. Bone microstructure was analyzed using micro-computed tomography and the contents of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase 5b (TRAP5b) were detected by enzyme-linked immunosorbent assay in serum. BMSC proliferation was measured by cell-counting kit (CCK)-8 assay. Alizarin red S (ARS) staining and ALP activity assay were performed to assess BMSC mineralization and calcification. The activity of the Wnt/β-catenin pathway was evaluated by dual-luciferase reporter assay.Results:Melatonin prevented bone loss in OVX mice. Melatonin increased ALP expression and reduced TRAP5b expression. HGF and β-catenin were downregulated, while PTEN was upregulated in the femur of OVX mice. Melatonin elevated HGF expression and then stimulated BMSC proliferation and osteogenic differentiation. Additionally, HGF diminished the expression of PTEN, resulting in activated Wnt/β-catenin pathway both in vitro and in vivo. Furthermore, melatonin was shown to ameliorate osteoporosis in OVX mice via the HGF/PTEN/Wnt/β-catenin axis.Conclusion:Melatonin could potentially enhance osteogenic differentiation of BMSCs and retard bone loss through the HGF/PTEN/Wnt/β-catenin axis.

The Effects of Berry Anthocyanin-Rich Diets for the Protection Against Ovariectomy-Induced Bone Loss

Abstract Objectives Osteoporosis is a condition of low bone mass that may affect women due to an abrupt cessation of ovarian hormones and increased level inflammation and oxidation. As the United States population increases and longevity rises, low bone mass that could lead to fractures poses an even greater health issue and cause for unnecessary health expenses. More and more, individuals are seeking alternatives such as functional foods as oppose to drug medications to attenuate the bone loss. Fruits like dried plums and certain berries are purported to have beneficial effects as strong antioxidants in retarding bone loss resulting from aging. To provide further in vivo evidence of blueberry effects and determine whether strawberry is supportive of bone health for the benefit of human consumption. The hypothesis of this study is that blueberry- and strawberry-rich diets will prevent or slow the progression of ovariectomy-induced bone loss in a rat model (Sprague Dawley) of osteoporosis. Methods We fed 15 estrogen-deficient female rats (3-month old) with either a blueberry-rich (10% w/w), strawberry-rich (10% w/w), or normal diet (Ovx), and 3 intact (Sham) rats a normal diet for 13 weeks. Upon sacrifice, we collected major organs, blood, vertebrae, femora, and tibiae for analysis. Three-point bending tests were performed using a compressive hydraulic system on the femora and tibiae to asses bone fracture point, stiffness, and elasticity. Tissue mineralization of the 6th lumbar vertebrae were measured as ratio of ash to dry weight burning at 800°C in a muffled furnace. Serum bone alkaline phosphatase and tartrate-resistant acid phosphatase 5b are being measured currently for presentation of results at the conference. Results There were no differences in body weight between groups at the start or termination of the study, nor were changes in body weight different (P > 0.05). Tissue mineralization trended to significance (P < 0.08) between Sham and Ovx groups, but not when comparing blueberry and strawberry groups to Ovx. The remaining data will be reported at the conference. Conclusions Thus far, we cannot conclude that berry-rich diets are sufficient to protect against ovariectomy-induced bone loss in female rats. Funding Sources The Agricultural Research Institute (ARI) of California State University.

Substrate composition and dimensionality direct osteocyte gene expression

Background Osteoporosis has become a major public health problem, it is characterised by loss of bone mass and architecture due to disturbance in bone remodelling. Most current treatments retard bone loss but have no stimulating effect on bone formation [1]. Osteocytes act as an orchestrator for bone modelling, and secrete the glycoprotein sclerostin which negatively regulates bone formation and is a potential novel drug target [2]. Due to difficulty of accessing and studying osteocytes in vitro, an osteocyte-like MLO-Y4 cell line was developed. However, these cells only secrete sclerostin in trace amounts [3]. The objective of this study was to develop a novel biomimetic environment that would stimulate MLO-Y4 to express the osteocyte specific Sost gene.

Effect of Milk Powder Supplementation with Different Calcium Contents on Bone Mineral Density of Postmenopausal Women in Northern China: A Randomized Controlled Double-Blind Trial.

The objective of this study is to examine the effect of milk powder supplementation with different calcium contents on bone mineral density (BMD) in postmenopausal Chinese women, and to determine a more appropriate dose of calcium supplementation. A 2-year, randomized controlled double-blind trial. Postmenopausal women (n = 210) aged 50-65 years were recruited and assigned randomly into three calcium supplementation groups. All participants received milk powder supplementation with different calcium contents (300, 600, and 900 mg per day for groups A, B, and C, respectively) and all groups received 800 IU of vitamin D per day. During the follow-up period, BMD of the left hip and lumbar spine (as the main indicator) was measured using dual-energy X-ray absorptiometry at the baseline, 1 and 2 years. Both three BMD measures and the changes of BMD over 2 years were used to analyze. Before adjusting for covariates, BMD in group A of the lumbar spine and groups A and B of greater trochanter decreased significantly from the baseline over time but increased significantly in the rest groups of the lumbar spine and greater trochanter and in three groups of Ward's triangle. There were significant differences across the three groups for changes of BMD in the greater trochanter and Ward's triangle. When adjusting for covariates, there were significant decreases with time in group A of the spine (P = 0.001), groups A and B of greater trochanter (P = 0.0002 and P = 0.04, respectively) and increases in groups B and C of Ward's triangle (P = 0.03 and P = 0.004, respectively). BMD change in the greater trochanter was significantly different among three groups. For healthy postmenopausal women, high calcium milk powder supplementation was better in retarding bone loss than medium and low calcium in the greater trochanter. Considering the dietary calcium intake of postmenopausal women in north of China, a dose of 900 mg/day is considered as the most appropriate calcium supplementation for greater trochanter but not for other sites.

The efficacy of calcium supplementation alone in elderly Thai women over a 2-year period: a randomized controlled trial

Supplementation with elemental calcium 500 mg/day alone for 2 years is able to decrease bone turnover and is effective in retarding bone loss at lumbar spine and slowing bone loss at femoral neck in elderly Thai women who had low dietary calcium intake. Most elderly Thais have a total dietary calcium intake of less than the recommended amount. The aim of the study was to investigate the effect of calcium supplementation on bone mineral density and biochemical indices of bone remodeling in Thai postmenopausal women. Four hundred and four healthy postmenopausal women 60 years old or older without osteoporosis were recruited and conducted in a randomized, double-blinded, placebo-controlled trial. They were randomly given elementary calcium 500 mg/day or placebo for 2 years. Dietary calcium intake was calculated from the nutrient compositional analysis of the 3-day food records. Serum 25 hydroxyvitamin D was measured by radioimmunoassay and bone turnover markers were determined by electrochemiluminescence immunoassay. The age of the subjects was 65.8 ± 4.4 years. All baseline characteristics of the subjects in the calcium-supplemented group and the placebo group were not statistically different. At the end of the study, significant decreases in serum C-terminal telopeptide of type I collagen and serum total procollagen type I amino terminal propeptide in the calcium-supplemented group were observed, while there was no change in the placebo group. In addition, plasma parathyroid hormone decreased, although not significantly, only in the calcium-supplemented group. Percent changes from baseline of lumbar spine (L2-L4) bone mineral density increased 2.76% in the calcium-supplemented group and 0.87% in the placebo group, whereas the percent changes from baseline of femoral neck decreased 0.21% in the calcium-supplemented group and 0.90% in the placebo group. Calcium supplementation is necessary for the decrease of bone turnover and prevention of bone loss in Thai elderly women.

Resistive vibration exercise retards bone loss in weight-bearing skeletons during 60 days bed rest

Countermeasures are desirable to retard bone loss during long-term space flight. We evaluated the effect of an intervention protocol on bed rest-induced bone loss. We developed a resistive vibration exercise (RVE) platform to test if an intervention RVE protocol would be effective to protect bed rest-induced bone loss. Fourteen male subjects were assigned randomly to either the RVE group (n = 7) that performed daily supervised resistive vibration exercise or to the no any exercise control (CON) group (n = 7). Both dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were used to monitor changes in bone mineral density. RVE significantly prevented bone loss at multiple skeletal sites, including calcaneus, distal tibia, hip, and lumbar spine (L2-L4). The ratio of urinary calcium and creatinine was found higher after starting bed rest in CON group while no significant changes were observed in RVE group. No significant temporal change was found for osteocalcin-N during and after bed rest in CON group. However, a significant increase was shown after bed rest in RVE group. In both groups, the urinary concentration of bone resorption markers, such as C-telopeptide of type I collagen (CTX-I) and deoxypyridinoline (DPD), were significantly elevated after bed rest. In the CON group, no significant temporal effect was found for hydroxyproline (HOP), CTX-I, and DPD during bed rest and the serum concentration of HOP and TGF-β significantly increased about 52.04% and 24.03%, respectively only after bed rest. However, all these markers tended to decrease in the RVE group. Our results might imply that the intervention of RVE retarded bone loss induced by simulated microgravity in humans that was mainly attributed to its anabolic effects.

Protein intake, calcium balance and health consequences

High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.

The role of Tai Chi Chuan exercise on osteoporosis prevention and treatment in postmenopausal women

Osteoporosis is a disease characterized by fragile bones and high susceptibility to low trauma fractures. Tai Chi, an ancient Chinese mind-body exercise that is reported to enhance muscle function, balance and flexibility, and to reduce pain, depression and anxiety, may safely and effectively be used to prevent or treat osteoporosis. The aim of this review is to evaluate the evidence for Tai Chi as an intervention to reduce rate of bone loss in postmenopausal women. A literature search on randomized controlled trials (RCTs), prospective cohort studies, and cross-sectional studies that included Tai Chi as an intervention, and had at least 1 outcome related to measurement of bone metabolism were identified in PubMed/Medline. Twenty-one controlled studies were identified in the database, which suggested Tai Chi slowed down the loss of bone mineral density in most postmenopausal women, improved balance and strength, relieves pain from arthritis, and improved mental strength so they can cope better with chronic diseases. Regular Tai Chi Chuan exercise is beneficial for retarding bone loss in the weight-bearing bones of postmenopausal women.

Bone loss during menopausal transition among southern Chinese women

ObjectivesEstrogen deficiency during menopausal transition is associated with rapid bone loss. The purpose of this study was to examine the time of onset, the rate, and predictors of menopausal bone loss. Study designProspective data were analyzed from 160 Chinese women between the ages of 45 to 55 years who participated in the Hong Kong Osteoporotic Study. Main outcome measuresAll participants were studied yearly for 4 years. Demographic information, menstrual status according to the Stages of Reproductive Aging Workshop (STRAW), and lifestyle habits were recorded as well as bone mineral density (BMD) measured every visit. Baseline follicular stimulating hormone, sex hormone binding globulin, parathyroid hormones, C-terminal telopeptides of type 1 collagen, estradiol and testosterone were also measured. ResultsThere was no significant bone loss at the spine, femoral neck and total hip in premenopausal women. Maximal bone loss occurred within the STRAW stage −2 and −1. Age at menopause, baseline age, body weight and FSH were independent predictors of bone loss. Subjects in the lowest quartile of baseline body weight (<50kg) lost bone 2 times faster at spine compared with those in the highest quartile (>61kg). Subjects in the highest quartile of baseline FSH (>40IU/l) lost bone 1.3–2.3 times faster at all 3 sites compared with those in the lowest quartile (<5.8IU/l). ConclusionStrategies to retard bone loss should be stressed to middle aged women, especially those with lean body built or with early menopause, to prevent osteoporosis later on in life.

Effect of community-based nutrition education intervention on calcium intake and bone mass in postmenopausal Vietnamese women

To examine the effect of community-based nutrition education intervention on calcium intake and bone mass in Vietnamese postmenopausal women. A controlled trial was conducted in two groups as intervention and control. The intervention group was given nutrition education during 18 months to improve calcium intake, while the control subjects had the usual diet. Calcium intake and bone mass were evaluated every 6 months. Bone mass was assessed by speed of sound (SOS) at calcaneus, referred to as quantitative ultrasound measurement. Anthropometric indices and serum parathyroid hormone (PTH) were determined at baseline and at the end of intervention. Two rural communes of Hai Duong province located in the Red River Delta in Vietnam. A total of 140 women aged 55-65 years, who were more than 5 years postmenopausal and with low calcium intake (<400 mg/d), were recruited. After 18 months of intervention, 108 women completed the study. Calcium intake in the intervention group had increased significantly (P < 0.01) while it had no significant changes in controls. SOS values were not changed significantly in the intervention subjects while it decreased significantly by 0.5 % in the controls (P < 0.01). The intervention led to a decrease in serum PTH by 12 % (P < 0.01). In the controls, there was an increase in serum PTH by 32 % (P < 0.001). Nutrition education intervention was effective in improving calcium intake and retarding bone loss in the studied subjects.

Gender-Dependent Reductions in Vertebrae Length, Bone Mineral Density and Content by Doxorubicin Are Not Reduced by Dexrazoxane in Young Rats: Effect on Growth Plate and Intervertebral Discs

Doxorubicin (DOX) is widely used in anti-cancer cocktails. Dexrazoxane (DXR) is a cardioprotectant approved for use with DOX. The effect of DOX, with or without DXR, on bone in children is not well understood. The aim of this study was to examine the effect of DOX on vertebrae and femur length and bone density acquisition in young rats, as well as to test the hypothesis that young females are more susceptible to DOX-induced tissue damage than young males. The results of this study suggest that a single injection of DOX in young female and not male rats is associated with low bone turnover resulting in vertebrae and femur bone growth deficits. DOX selectively decreased BMD and BMC accrual in the lumbar vertebrae that was not prevented by DXR. DOX-treated rats also exhibited growth plate and intervertebral disc defects. This information will be useful in the design of interventions to promote bone growth or retard bone loss during DOX treatment.

A randomized, prospective study of the effects of Tai Chi Chun exercise on bone mineral density in postmenopausal women

Chan K, Qin L, Lau M, Woo J, Au S, Choy W, Lee K, Lee S. A randomized, prospective study of the effects of Tai Chi Chun exercise on bone mineral density in postmenopausal women. Arch Phys Med Rehabil 2004;85:717–22. Objective To evaluate the potential benefits of programmed Tai Chi Chun (TCC) exercise on the weight-bearing bones of early postmenopausal women. Design Age-matched and randomized prospective intervention. Setting University medical school. Participants One hundred thirty-two healthy postmenopausal women (mean age, 54.0±3.5y) within 10 years of menopause onset were recruited and randomized into the TCC exercise group (n=67) or the sedentary control group (n=65). Intervention Supervised TCC exercise was performed by the TCC group for 45 minutes a day, 5 days a week, for 12 months; control subjects retained a sedentary life style. Main outcome measures Bone mineral density (BMD) was measured in the lumbar spine and proximal femur by using dual-energy x-ray absorptiometry and in the distal tibia by using multislice peripheral quantitative computed tomography (pQCT). All BMD measurements were repeated after 12 months in both groups. Fracture rate was also documented. Results Baseline measurements showed homogeneity in age, anthropometric variables, and menstruation status between the TCC and control groups. Exactly 81.6% of the subjects in the TCC group and 83.1% of subjects in the control group completed the 12-month follow-up study. BMD measurements revealed a general bone loss in both TCC and sedentary control subjects at all measured skeletal sites, but with a reportedly slower rate in the TCC group. A significant 2.6- to 3.6-fold retardation of bone loss ( P<.01) was found in both trabecular and cortical compartments of the distal tibia in the TCC group as compared with the controls, as measured by pQCT. A total of 4 fracture cases were documented during follow-up, including 3 subjects in the control group and 1 in the TCC group. Conclusions This is the first prospective and randomized study to show that a programmed TCC exercise intervention is beneficial for retarding bone loss in weight-bearing bones in early postmenopausal women. Long-term follow-up is needed to substantiate the role of TCC exercise in the prevention of osteoporosis and its related fracture.

Nutritional Approaches to Late Toxicities of Adjuvant Chemotherapy in Breast Cancer Survivors

Adjuvant chemotherapy of breast cancer reduces recurrence rates and prolongs survival at the cost of both acute and chronic toxicities. Breast cancer survivors who have received adjuvant chemotherapy may suffer from late effects of chemotherapy including congestive heart failure, neuropathy, premature menopause, and osteoporosis. Nutritional approaches to these problems are distinct in their orientation and success. Study of free radical scavengers for anthracycline-induced cardiomyopathy was born from known pathogenetic mechanisms of cardiotoxicity but has been universally disappointing thus far in clinical trials. Application of agents used for diabetic neuropathy suggests that evening primrose oil, alpha-lipoic acid, and capsaicin may all play a role in the empiric options available to patients with chemotherapy-induced neuropathy. Plant-derived preparations including black cohosh (Actaea racemosa), dong quai (Angelica sinensis), evening primrose (Oenothera biennis), and red clover (Trifolium pretense) are used by patients experiencing hot flashes due to premature menopause despite a paucity of clinical trial data demonstrating either safety or efficacy. Calcium and vitamin D are widely accepted as an effective means to retard bone loss leading to osteoporosis. Nutritional approaches to late effects of breast cancer chemotherapy offer the prospect of preventing or ameliorating these sequelae of treatment. However, except for vitamin D and calcium for prevention of bone loss, current clinical evidence supporting use of nutritional agents remains sparse.

Tai Chi Retards Bone Loss and Improves Muscle Strength

"Tai Chi Retards Bone Loss and Improves Muscle Strength." The Physician and Sportsmedicine, 31(4), pp. 16–17

Regular Tai Chi Chuan exercise may retard bone loss in postmenopausal women: A case-control study

Qin L, Au S, Choy W, Leung P, Neff M, Lee K, Lau M, Woo J, Chan K. Regular Tai Chi Chuan exercise may retard bone loss in postmenopausal women: a case-control study. Arch Phys Med Rehabil 2002;83:1355-9. Objective: To evaluate the potential benefits of regular Tai Chi Chuan exercise on the weight-bearing bones of postmenopausal women. Design: Case-control study. Setting: University medical school in Hong Kong. Participants: Postmenopausal women (age range, 50–59y), including 17 self-selected regular Tai Chi Chuan exercisers (TCE) with over 4 years of regular exercise, and 17 age- and gender-matched nonexercising controls (CON). Interventions: Not applicable. Main Outcome Measures: Bone mineral density (BMD) in the lumbar spine and proximal femur was measured at baseline and at follow-up 12 months later by using dual-energy x-ray absorptiometry (DXA) and in the distal tibia using multislice peripheral quantitative computed tomography (pQCT). Results: Baseline results showed that the TCE group had significantly higher BMD (10.1%–14.8%, all P<.05) than the CON group in the lumbar spine, proximal femur, and the ultradistal tibia. The follow-up measurements showed generalized bone loss in both groups. Although both DXA and pQCT measurements revealed decelerated rates of bone loss in the TCE group, only the more sensitive pQCT showed significantly reduced rate of bone loss in trabecular BMD of the ultradistal tibia (TCE vs CON: −1.10%±1.26% vs −2.18%±1.60%, P<.05) and of cortical BMD of the distal tibial diaphysis (TCE vs CON: −0.90%±1.36% vs −1.86%±0.93%, P<.05). Conclusion: This is the first case-control study to show that regular Tai Chi Chuan exercise may help retard bone loss in the weight-bearing bones of postmenopausal women. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Estrogens and bone health in men.

It has generally been held that estrogen and testosterone are the major sex steroids regulating bone metabolism in women and men, respectively. However, the description of several "experiments of nature" led to a reconsideration of this notion. Thus, a male carrying homozygous mutations in the ER-alpha gene and two males with homozygous mutations in the aromatase gene had osteopenia, unfused epiphyses, and elevated indices of bone turnover. Though these findings indicated that estrogen plays a role in regulating the male skeleton, they left unresolved the issue of whether estrogen acted on the male skeleton mainly to enhance bone mass acquisition during growth and maturation, or whether it also acted to retard bone loss in aging individuals. To address this issue, several cross-sectional observational studies have related bone mineral density (BMD) to sex steroids in elderly men, and found that estrogen correlated better than testosterone with BMD. In addition, recent longitudinal studies from our group indicate that bioavailable estrogen correlated better than testosterone both with the gain in BMD in young men and with loss of BMD in elderly men. These observational studies do not, however, prove causality, which requires direct interventional studies. Thus, we eliminated endogenous testosterone and estrogen production in 59 elderly men (mean age 68 years), studied them first under conditions of physiologic testosterone and estrogen replacement, and then assessed the impact on bone turnover of withdrawing both testosterone and estrogen, withdrawing only testosterone, only estrogen, or continuing both. We found that estrogen played the major role in regulating bone resorption in these men, and that both estrogen and testosterone were important in maintaining bone formation. Collectively then, these findings indicate that estrogen plays a dominant role in regulating the male skeleton.

How to prevent fractures in the individual with osteoporosis.

The high rate of osteoporotic fracture in Western populations has resulted in a significant burden in terms of morbidity, mortality and health care costs. The use of DXA has made the diagnosis of osteoporosis easier and identified a subgroup of individuals who are at a higher risk of fracture. It is a useful tool in determining therapy in those at greatest risk of fracture. However, widespread use of such treatments is low and greater uptake remains an elusive goal. There are now many different treatments that reduce fracture rate, and can accompany lifestyle measures such as smoking cessation, diet and exercise. Dietary supplementation with calcium has been shown to reduce the risk of vertebral fracture, and the combination of calcium with vitamin D has been shown to reduce fracture at non-vertebral sites, including the hip. Although ERT, SERMs and tibolone all retard bone loss, prospective fracture prevention has only been shown for SERMs and then only at the spine. Bisphosphonates represent a class of potent anti-resorptive agents, which have been shown to reduce fracture rate at vertebral and non-vertebral sites. Other agents such as calcitonin, PTH and fluoride are of less certain benefit in preventing fracture.

Calcium bioavailability: an in vivo assessment

Calcium supplementation in the form of various salts has been used in humans and in experimental animals to retard bone loss and lower blood pressure, but there are few data in regard to the bioavilabilty of these salts in the in vivo system. Our study evaluated the effect of extra calcium supplementation in the form of three different calcium salts (i.e. calcium carbonate, (CaC) calcium lactate (CaL), and calcium phosphate (CaP) in normocalcemic and hypocalcemic status of the in vivo milieu. The male wistar rats were divided in two groups, normocalcemic and hypocalcemic (induced by vit. D deficiency). Both the groups were supplemented with extra 1.6% calcium in the form of either of these salts. The animals were screened every 4 weeks for the changes observed in the impetus in their growth (as observed by the gain in their body weight.), and the circulating levels of calcium (Ca), phosphorous (P), and magnesium (Mg) and alkaline phosphatase activity, and all these animals were sacrificed at 12 weeks after being on the high Ca, diet to study the bone mineral content. CaC supplementation for long time has shown hypercalcemic, hypomagnesemic and hypophosphatemic tendencies. CaL supplementation showed better results as compared with CaC supplementation. CaP supplementation did show some tendencies towards lowering of serum magnesium levels. However of the three salts selected for bioavailablity assessment and analyzed for the parameters mentioned above, CaP seems to be a better supplement for the in vivo system compared to CaL and CaC.

Epidemiology of Osteoporosis

This review has shown that osteoporosis is a major public health problem because of its association with fracture. It is now possible to predict future risk of fracture by measuring BMD with noninvasive techniques. The relation between BMD and fracture is comparable to that between blood pressure and stroke such that fracture risk can be assessed from a definition of osteoporosis using bone mass and past history of fracture. Because some of the risk factors for peak bone mass, involutional bone loss, and fracture are now characterized, coupled with innovative agents capable of retarding bone loss, it is becoming possible to generate preventive strategies, for the entire population as well as for those at highest risk.