New advances in osteoporosis nutritional prevention

With the human race experiencing a progressive increase in life expectancy, we are facing a growing prevalence of chronic age-related conditions, among which osteoporosis is a generalised condition of bone, whose hallmark is increased bone fragility. Based on the overwhelming body of evidence emphasising that gonadal failure at the time of menopause causes osteopenia and the administration of estrogens in postmenopausal women prevents this loss, hormone replacement therapy (HRT) has been widely recommended. However HRT should be limited due to its potential adverse effects. In this light, an effort should be made to integrate alternative therapies of proven values to provide new options for women in midlife. Research in nutrition over the past 30 years has led to exciting and significant progress. Although the primary role of diet is to provide sufficient nutrients to fulfill the metabolic requirements of an individual, there is an emerging rationale to support the hypothesis that, by modulating specific target functions in the body, diet can help to achieve optimal health and also play an important role in reducing the risk of disease. Specifically, it has been recognized that human diet contains, in addition to essential macro- and micronutrients, a complex array of naturally occurring bioactive molecules, the phytochemicals, that may confer significant long-term health benefits. Indeed, besides calcium, micronutrients such as vitamins, polyphenols, phytoestrogens, trace elements or minerals remain a source for putative new and innovative dietary health intervention in the nutritional prevention of osteoporosis.     

Relevance of osteoporosis in women with fracture of the femoral neck.

A prospective study of fractures of the femoral neck was conducted over 12 months in order to ascertain the relevance of generalised osteoporosis as determined by metacarpal morphometry. A series of some 200 women sustaining a fracture of the femoral neck after minor trauma had bone mass measurements similar to those of a control population of normal women, and 16% were not osteoporotic. A history of previous fractures was documented in one third of the women, but this was unrelated to the presence or severity of osteoporosis, although over half of the fractures had occurred within the previous four years. Trochanteric fractures were seen more commonly in severely osteoporotic women (p less than 0.005), whereas cervical fractures predominated in those who were not osteoporotic. These findings support the hypothesis that postural instability is the major determinant for femoral neck fracture and that generalised osteoporosis, rather than being a prerequisite for fracture, merely determines the type of fracture sustained.     

The role of i.v. ibandronate administration in osteoporosis therapy

Osteoporosis is a chronic disease of the osseous system characterised by decreased strength of bone tissue, which in turn leads to increased fracture risk. It has been demonstrated that osteoporosis affects more than 30% of women after the menopause (World Health Organization, 1994). However, the disease is also observed in men. The primary goals of osteoporosis therapy include prevention of low-energy fractures and general improvement of quality of life. Any patient with diagnosed osteoporosis requires, besides prevention, the application of proper treatment. Of the available therapeutic options, the best are bisphosphonates, medical agents with well identified properties, therapeutic efficacy, and safety which has been confirmed in many clinical studies. Therefore, they are recommended as first line drugs for osteoporosis. The efficacy of oral preparations may be limited, due to low bioavailability, complications and adverse effects from the gastrointestinal tract. So the parenteral administration of bisphosphonates is a valuable alternative. A fine example of such therapy is the intravenous administration of ibandronate. Short injection time periods and the relatively long, three-month intervals between administrations are unquestionable advantages of this therapy mode. In addition, the therapy does not constrain a patient's everyday activity, and simultaneously provides regular contact with doctors and the therapeutic centre. Additionally, a good tolerance of the drug and its high therapeutic efficacy, proven by appreciably reduced fracture risks, significantly improves the quality of life of patients suffering from osteoporosis. This paper is a thorough review of current knowledge on the efficacy and safety of i.v. ibandronate in osteoporosis therapy, as presented in the latest literature reports.     

Recommendations on the management of fragility fracture risk in women younger than 70 years

The risk for fragility fracture represents a problem of enormous magnitude. It is estimated that only a small fraction of women with this risk take the benefit of preventive measures. The relationship between estrogen and bone mass is well known as they are the other factors related to the risk for fracture. There are precise diagnostic methods, including a tool to diagnose the risk for fracture. Yet there continues to be an under-diagnosis, with the unrecoverable delay in instituting preventive measures. Women under the age of 70 years, being much more numerous than those older, and having risk factors, are a group in which it is essential to avoid that first fragility fracture. Today it is usual not to differentiate between the treatment and the prevention of osteoporosis since the common aim is to prevent fragility fractures. Included in this are women with osteoporosis or with low bone mass and increased risk for fracture, for whom risk factors play a primary role. There is clearly controversy over the type of treatment and its duration, especially given the possible adverse effects of long-term use. This justifies the concept of sequential treatment, even more so in women under the age of 70, since they presumably will need treatment for many years. Bone metabolism is age-dependent. In postmenopausal women under 70 years of age, the increase in bone resorption is clearly predominant, related to a sharp drop in estrogens. Thus a logical treatment is the prevention of fragility fractures by hormone replacement therapy (HRT) and, in asymptomatic women, selective estradiol receptor modulators (SERMs). Afterwards, there is a period of greater resorption, albeit less intense but continuous, when one could utilise anti-resorptive treatments such as bisphosphonates or denosumab or a dual agent like strontium ranelate. Bone formation treatment, such as parathyroid hormone (PTH), in women under 70 years will be uncommon. That is because it should be used in cases where the formation is greatly diminished and there is a high risk for fracture, something found in much older women.     

The role of i.v. ibandronate administration in osteoporosis therapy

Osteoporosis is a chronic disease of the osseous system characterised by decreased strength of bone tissue, which in turn leads to increased fracture risk. It has been demonstrated that osteoporosis affects more than 30% of women after the menopause (WHO, 1994). However, the disease is also observed in men. The primary goals of osteoporosis therapy include prevention of low-energy fractures and general improvement of quality of life. Any patient with diagnosed osteoporosis requires, besides prevention, the application of proper treatment. Of the available therapeutic options, the best are bisphosphonates, medical agents with well identified properties, therapeutic efficacy, and safety which has been confirmed in many clinical studies. Therefore, they are recommended as first line drugs for osteoporosis. The efficacy of oral preparations may be limited, due to low bioavailability, complications and adverse effects from the gastrointestinal tract. So the parenteral administration of bisphosphonates is a valuable alternative. A fine example of such therapy is the intravenous administration of ibandronate. Short injection time periods and the relatively long, three-month intervals between administrations are unquestionable advantages of this therapy mode. In addition, the therapy does not constrain a patient's everyday activity, and simultaneously provides regular contact with doctors and the therapeutic centre. Additionally, a good tolerance of the drug and its high therapeutic efficacy, proven by appreciably reduced fracture risks, significantly improves the quality of life of patients suffering from osteoporosis. This paper is a thorough review of current knowledge on the efficacy and safety of i.v. ibandronate in osteoporosis therapy, as presented in the latest literature reports.     

Clinical practice guidelines for the care and treatment of breast cancer: 14. The role of hormone replacement therapy in women with a previous diagnosis of breast cancer

Objective

To provide information and recommendations to women with a previous diagnosis of breast cancer and their physicians regarding hormone replacement therapy (HRT).

Outcomes

Control of menopausal symptoms, quality of life, prevention of osteoporosis, prevention of cardiovascular disease, risk of recurrence of breast cancer, risk of death from breast cancer.

Evidence

Systematic review of English-language literature published from January 1990 to July 2001 retrieved from MEDLINE and CANCERLIT.

Recommendations

· Routine use of HRT (either estrogen alone or estrogen plus progesterone) is not recommended for women who have had breast cancer. Randomized controlled trials are required to guide recommendations for this group of women. Women who have had breast cancer are at risk of recurrence and contralateral breast cancer. The potential effect of HRT on these outcomes in women with breast cancer has not been determined in methodologically sound studies. However, in animal and in vitro studies, the development and growth of breast cancer is known to be estrogen dependent. Given the demonstrated increased risk of breast cancer associated with HRT in women without a diagnosis of breast cancer, it is possible that the risk of recurrence and contralateral breast cancer associated with HRT in women with breast cancer could be of a similar magnitude. · Postmenopausal women with a previous diagnosis of breast cancer who request HRT should be encouraged to consider alternatives to HRT. If menopausal symptoms are particularly troublesome and do not respond to alternative approaches, a well-informed woman may choose to use HRT to control these symptoms after discussing the risks with her physician. In these circumstances, both the dose and the duration of treatment should be minimized.

Validation

Internal validation within the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer; no external validation.

Sponsor

The steering committee was convened by Health Canada.

Completion date

October 2001.Hormone replacement therapy (HRT) connotes treatment with either estrogen alone or estrogen with progesterone in postmenopausal women. Menopausal symptoms, such as hot flashes and vaginal dryness, and the potential long-term effects of estrogen deprivation are a concern to women with breast cancer, particularly those in whom menopause develops early as a result of adjuvant chemotherapy.Traditionally, the use of HRT has been contraindicated in women with breast cancer because of the notion that the development and growth of breast cancer is estrogen dependent and that the introduction of HRT may increase the risk of breast cancer recurrence. The focus of this guideline is on whether it is safe to give HRT to women with breast cancer.     

Hormone replacement therapy: a survey of Ontario physicians' prescribing practices

BACKGROUND: Although much has been written about hormone replacement therapy (HRT), there are few clearcut recommendations on its use. The purpose of this study was to determine Ontario physicians'' patterns of and reasons for prescribing HRT, their use of pretreatment investigations and their surveillance of HRT users, and to determine whether physicians'' reported practice is consistent with existing recommendations. METHODS: A self-administered questionnaire was mailed to a nonproportional stratified sample of 327 Ontario physicians (23.9% gynecologists, 76.1% general practitioners/family physicians [GP/FPs]). Outcome measures were ranking of reasons for prescribing HRT, nature of preliminary testing, regimens prescribed, duration of HRT and frequency of follow-up. RESULTS: The response rate was 60.9% overall (70.9% of the gynecologists, 58.3% of the GP/FPs). Prevention of osteoporosis was reported by 97.4% as an important or very important reason for prescribing HRT; prevention of coronary artery disease was important or very important for 89.3%. When considering whether or not to prescribe HRT, 97.3% stated that breast cancer was an important or very important factor. When presented with hypothetical cases, 97.0% stated that they would prescribe combined estrogen-progestin for a symptomatic woman with an intact uterus; 13.6% stated that they would do so for a woman with no uterus. Most reported that they would prescribe HRT for 12 or more years (73.3%) and would follow up patients every 1 to 2 years (70.6%). INTERPRETATION: Despite controversy about HRT in the published literature, the Ontario physicians surveyed reported similar reasons and patterns of prescribing, pretreatment investigations, and surveillance of postmenopausal women using HRT. These results suggest that Ontario physicians'' knowledge about HRT is consistent with recommendations in the published literature.     

Anti-atherosclerotic and anti-diabetic properties of probucol and related compounds

Probucol is a diphenolic compound with anti-oxidant and anti-inflammatory properties that reduces atherosclerosis and restenosis. Unfortunately, adverse effects on blood lipoproteins and cardiac electrophysiology have curtailed its use as a drug. Compounds related to probucol that have improved efficacy without the adverse effects offer promise as novel therapies of cardiovascular disease. Recent results suggest that these compounds may be used for the prevention of type 2 diabetes, a disease that is increasing in prevalence and importance world-wide. In this review, the molecular mechanisms underlying the beneficial activities of probucol and related compounds are described.     

Hormone replacement therapy,calcium and vitamin D<Subscript>3</Subscript> versus calcium and vitamin D<Subscript>3</Subscript>alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456]

This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.     

Hormone replacement therapy and cardiovascular disease

This year's work on hormone replacement therapy (HRT) and cardiovascular disease has been remarkable for the publication of the first randomised controlled trial of HRT use, the Heart Estrogen Replacement Study (HERS). The findings go against not only the trend of previous observational epidemiological studies, but also against findings in the very many studies which have previously shown and continue to show this year a beneficial effect of HRT on a large variety of cardiovascular risk factors, including endothelial function, here reviewed. The aspect of the effect of HRT on clotting variables is clearly crucial given the increased risk of venous thrombosis, and also increased number of cardiac events in the first 4 months of the HERS. Prothrombotic factors increase with age in women, and HRT alters these, particularly fibrinogen, factor VII, and PAI (less change with transdermal HRT) and antithrombin III. In normal women therefore the balance should be towards fibrinolysis rather than coagulation. Work has been presented in abstract for clarifying the effects of HRT on coagulation markers and grasping the problem of differences according to its route of administration. The full publications on this work are expected shortly. We are still awaiting evidence from randomized controlled trials of HRT in primary prevention; one is now recruited but will not report until 2005.     

Sex steroids,ANGELS and osteoporosis

Osteoporosis is characterized by reduced bone density and strength. Bone mass peaks between age 30 and 40 and then declines. This can be accelerated by factors including menopause and insufficient dietary calcium. Hormone replacement therapy (HRT) is currently the standard treatment for osteoporosis. However, growing concern over potential side effects of HRT has driven a search for alternative therapies. A recent report 1 reveals a potential alternative to HRT: a gender-neutral synthetic steroid that increases bone mass and strength without affecting reproductive organs. This compound acts via a novel extranuclear sex steroid receptor signaling mechanism that has important implications for nuclear receptor biology and human health.     

Vascular effects of aromatase inhibitors: data from clinical trials

Aromatase inhibitors (AIs) are becoming the endocrine treatment of first choice for postmenopausal women with hormone receptor-positive breast cancer and are under investigation for use in breast cancer prevention. AIs reduce circulating estrogen to barely detectable concentrations. It is possible that such a low concentration will be deleterious to the vascular system since estrogen receptors are known to be in the cell walls of blood vessels and estrogen is thought to be important in maintaining blood vessel integrity. Because most women who present with primary breast cancer are cured by surgery and systemic therapy and the major cause of female death is vascular disease, it is particularly important to investigate the vascular side effects of AIs in current breast cancer adjuvant and prevention trials. In order to set the vascular toxicities of AIs reported in the current adjuvant trials into context, here we compare them with the toxicities seen during treatment with hormone replacement therapy (HRT) and selective estrogen receptor modulators (SERMs). Clinical trial evidence indicates that HRT increases risk of coronary heart disease (CHD) whereas SERMs and AIs (to date) appear to be neutral. Cerebrovascular disease and venous thromboembotic events are increased by HRT and SERMs but appear to be unaffected by treatment with AIs. Cognitive function is also considered here since it may also have a vascular component and is potentially a serious potential side effect/benefit of AIs. Recent studies indicate that HRT has a small detrimental effect on cognitive function and is associated with a doubling of the incidence of dementia. A comprehensive study of the SERM, raloxifene, on cognitive function showed no significant effect. There are no definitive reported studies investigating tamoxifen and none for AIs on cognitive function, although there is one in progress in the context of the IBIS II prevention trial which compares anastrozole to placebo in women at high risk. At present concerns about deleterious vascular side effects are confined to HRT and SERMs. However, we have few long-term data using AIs for the treatment and prevention of breast cancer.     

绝经后骨质疏松运动疗法的研究进展

绝经后骨质疏松是一种发生于绝经后妇女的慢性骨代谢疾病,目前其治疗还主要靠药物,但长期使用药物的一些副作用使一些患者不愿意采用药物疗法。因此,其治疗和预防目前仍具有挑战,正日益成为一个公众健康问题。体育运动是防治绝经后骨质疏松的一种非药物疗法,由于其简便、副作用少,近年来备受医患人员的亲睐。本文在查阅国内外相关文献的基础上,对有氧运动、抗阻力运动、平衡和本体感受训练、振动训练和水中训练等不同运动疗法在绝经后骨质疏松防治中的研究进展进行了综述。     

Estrogen,Progesterone and Epithelial Ovarian Cancer

Ovarian carcinoma (OCa) continues to be the leading cause of death due to gynecologic malignancies and the vast majority of OCa is derived from the ovarian surface epithelium (OSE) and its cystic derivatives. Epidemiological evidence strongly suggests that steroid hormones, primarily estrogens and progesterone, are implicated in ovarian carcinogenesis. However, it has proved difficult to fully understand their mechanisms of action on the tumorigenic process. New convincing data have indicated that estrogens favor neoplastic transformation of the OSE while progesterone offers protection against OCa development. Specifically, estrogens, particularly those present in ovulatory follicles, are both genotoxic and mitogenic to OSE cells. In contrast, pregnancy-equivalent levels progesterone are highly effective as apoptosis inducers for OSE and OCa cells. In this regard, high-dose progestin may exert an exfoliation effect and rid an aged OSE of pre-malignant cells. A limited number of clinical studies has demonstrated efficacies of antiestrogens, aromatase inhibitors, and progestins alone or in combination with chemotherapeutic drugs in the treatment of OCa. As a result of increased life expectancy in most countries, the number of women taking hormone replacement therapies (HRT) continues to grow. Thus, knowledge of the mechanism of action of steroid hormones on the OSE and OCa is of paramount significance to HRT risk assessment and to the development of novel therapies for the prevention and treatment of OCa.     

Anti-atherosclerotic and anti-diabetic properties of probucol and related compounds

Abstract

Probucol is a diphenolic compound with anti-oxidant and anti-inflammatory properties that reduces atherosclerosis and restenosis. Unfortunately, adverse effects on blood lipoproteins and cardiac electrophysiology have curtailed its use as a drug. Compounds related to probucol that have improved efficacy without the adverse effects offer promise as novel therapies of cardiovascular disease. Recent results suggest that these compounds may be used for the prevention of type 2 diabetes, a disease that is increasing in prevalence and importance world-wide. In this review, the molecular mechanisms underlying the beneficial activities of probucol and related compounds are described.     

The prospective evaluation of the osteoporotic vertebral fractures incidence in a random population sample

Introduction Osteoporotic vertebral fractures are mostly incidental but in some patients may lead to clinical symptoms, characteristic deformations of the vertebral column and increase total mortality. The aim of the study was to evaluate the prevalence of osteoporotic vertebral fractures and risk factors for osteoporosis in a random sample of Szczecin inhabitants aged over 50 in the relation to the whole European population examined in the frame of EVOS (European Vertebral Osteoporosis Study) and its prospective phase - EPOS (European Prospective Osteoporosis Study). At the baseline, 607 persons were studied, including 301 women and 306 men. Material and methods The questionnaire on the risk factors for osteoporosis and the spine X-rays analysed by morphometry, were taken in all subjects. The incidence of osteoporotic vertebral deformity in the studied population was similar in both sexes (12.6% women and 10,3% men) but in men aged 50-64 fracture incidence was significantly higher in comparison with women. The prevalence of new vertebral fractures examined after 4 years was higher in women than in men (9.1 vs 6.4/1000 persons years). Among the risk factors for osteoporosis, low physical activity and prolonged immobilization in women significantly influenced the incidence of vertebral deformities. Conclusions: 1) The study shows the high incidence of risk factors and osteoporotic vertebral deformities in the population of Szczecin inhabitants aged over 50. 2) Visual assessment only with a combination with morphometry is an optimal tool for detection of incident vertebral fractures.     

Influence of postmenopausal hormone replacement therapy on an estrogen metabolite biomarker of risk for breast cancer.

Whether postmenopausal hormone-replacement therapy (HRT) increases the risk of breast cancer remains controversial, despite numerous epidemiological studies. We approached the question from a biochemical rather than an epidemiological direction - we hypothesized that if estrogen administration increases the risk of breast cancer, it should also alter a known estrogen biomarker of risk towards what has been observed in patients who already have breast cancer. The specific biomarker we studied was the ratio of the urinary excretion of two principal estradiol metabolites, 2-hydroxyestrone and 16 alpha-hydroxyestrone, which is markedly decreased in women with breast cancer and women with familial risk for breast cancer. We studied 34 healthy postmenopausal women not on HRT and 19 women on HRT (Premarin 0.625 mg daily plus Provera, 2.5 mg daily, in women with a uterus and Premarin alone in women without a uterus); treatment duration ranged from 3 months to 15 years. We also studied four women with recently diagnosed, untreated breast cancer. The women with breast cancer showed a significantly lower 2-hydroxyestrone to 16 alpha-hydroxyestrone ratio than control women on HRT (1.35 +/- 0.13 vs. 2.71 +/- 0.84; p < 0.0001). There was no significant difference in the metabolite ratio between healthy women on HRT and women not on HRT (2.82 +/- 0.92 vs. 2.71 +/- 0.84). There was no significant difference between women receiving Premarin alone and women receiving Premarin plus Provera (2.46 +/- 0.84 vs. 3.13 +/- 0.90), and neither differed significantly from women not on HRT (2.71 +/- 0.84). The finding that the ratio of women on HRT was not decreased to or toward the ratio in women with breast cancer can be interpreted, we believe, as a suggestive item of biochemical evidence that HRT is not a risk for breast cancer.     

Behandeling van osteoporose bij ouderen: wat is de evidence?

Many older people, especially women, and their doctors still see osteoporosis as part of the natural course of ageing instead of as a preventable or treatable disorder. Height loss, hyperkyphosis, back pain, and fractures are accepted as consequences of ageing. The notion that it is too late to start treatment in a late stage of the disease forms another barrier to treatment. Although most studies of fracture reduction with medical treatment were not designed for the "geriatric" population, the average age of participants in most clinical trials was about 70 years. In all major studies patients also received calcium and vitamin D supplements. Nowadays, clinicians can choose from several effective treatments for the prevention of osteoporotic fractures in high-risk postmenopausal women. Data on the anti-fracture potential of calcium/vitamin D, raloxifene, bisphosphonates, strontium ralenate, and parathyroid hormone are now available. Bisphosphonates and strontium ralenate are good choices for first- or second-line treatment, while for the time being parathyroid hormone should only be used for the second-line treatment of osteoporosis in the elderly.     

The therapeutic effects of alfacalcidol on bone strength, muscle metabolism and prevention of falls and fractures

Established osteoporosis in older patients of both sexes is characterized by decoupled bone remodelling induced by sex hormone deficits and by somatopause, but also by lack of vitamin D and reduced synthesis of the D-Hormone (calcitriol; 1.25 (OH)2D) in the kidneys and bone, as well as from lack of receptors and/or receptor affinity for D-Hormone in the target organs. Parallel to the decreased bone strength a loss of muscle power occurs, together with an increase in balance disorders and an increasing risk of "intrinsic", nonsyncopal locomotoric falls. In alfacalcidol therapy, D-Hormone is provided to the body in circumvention of its own regulation, by means of which higher hormone concentrations can be achieved in the target tissues than by administration of plain vitamin D. In vitro and in vivo experiments have provided growing evidence that D-Hormone analogs tend to normalize PTH, lead to an increase in the number and activity of osteoblasts, reduce the activity of osteoclasts, and might thus normalize the "high bone turnover" in elderly osteoporotic patients ("supercoupling"). In addition, it has been shown that D-Hormone analogs are able to increase muscle power and walking distance in elderly D-Hormone deficient patients. Besides the known effect on the vertebral fracture rate, new clinical data confirm that D-Hormone analogs might reduce peripheral fractures by reducing falls. The expanded understanding of the pathogenesis of glucocorticoid- induced osteoporosis with its disturbed calcium homeostasis and the pharmacological effects of alfacalcidol, which counteract such iatrogenic bone loss, contribute to the understanding of its clinical efficacy in this most frequent form of secondary osteoporosis. Due to its recently discovered immunomodulating properties, alfacalcidol might find a slot in the management of bone loss caused by chronic inflammatory diseases or by organ transplantations. Alfacalcidol has multifactorial effects, among which the best known are its anti-bone loss and anti-fracture efficacies in postmenopausal osteoporosis. This demonstrated efficacy is related to its involvement in bone remodelling, leading to an improved bone strength. Its mode of action on muscle power, which reduces falls, is unique, differentiating this form of therapy from all other anti-osteoporotic drugs, none having demonstrated any influence on falls.