Prevention and treatment of osteoporosis

Osteoporosis develops in older adults when the normal processes of bone formation and resorption become uncoupled or unbalanced, resulting in bone loss. Fractures are the result of decreased bone mass and strength and, in the case of wrist and hip fractures, usually involve a fall. Osteoporosis prevention and treatment programs should then focus on strategies that minimize bone resorption and maximize bone formation as well as on strategies that reduce falls. Optimal treatment and prevention of osteoporosis require modification of risk factors, particularly smoking cessation, adequate physical activity, and attention to diet, in addition to pharmacologic intervention. A number of pharmacologic options are now available to health care providers. This article focuses on US Food and Drug Administration--approved medications for osteoporosis and emphasizes the importance of using these agents as part of a comprehensive program that includes nonpharmacologic measures, complete diagnostic evaluation, and adequate follow-up with bone mineral density measurement.     

Prevention and treatment of osteoporosis

Osteoporosis develops in older adults when the normal processes of bone formation and resorption become uncoupled or unbalanced, resulting in bone loss. Fractures are the result of decreased bone mass and strength and, in the case of wrist and hip fractures, usually involve a fall. Osteoporosis prevention and treatment programs should then focus on strategies that minimize bone resorption and maximize bone formation as well as on strategies that reduce falls. Optimal treatment and prevention of osteoporosis require modification of risk factors, particularly smoking cessation, adequate physical activity, and attention to diet, in addition to pharmacologic intervention. A number of pharmacologic options are now available to health care providers. This article focuses on US Food and Drug Administration-approved medications for osteoporosis and emphasizes the importance of using these agents as part of a comprehensive program that includes nonpharmacologic measures, complete diagnostic evaluation, and adequate follow-up with bone mineral density measurement.     

Cathepsin K inhibitors: a novel target for osteoporosis therapy

Osteoporosis is characterized by low bone mass with skeletal fragility and an increased risk of fracture. This bone loss is brought about by an imbalance between bone resorption and formation. Cathepsin K is the most abundant cysteine protease expressed in the osteoclast and is believed to be instrumental in bone matrix degradation necessary for bone resorption. Cathepsin K inhibitors represent a novel target for developing agents to treat osteoporosis and other disorders characterized by increased bone resorption.     

Denosumab for the management of postmenopausal osteoporosis

View the National Osteoporosis Foundation Clinician's Guide Postmenopausal osteoporosis is a major concern to public health. Fractures are the major clinical consequence of osteoporosis and are associated with substantial morbidity, mortality, and health care costs. Despite the availability of screening and treatment guidelines, osteoporosis diagnosis and treatment remain low. Health care providers may consult guidelines in the clinical management of their patients with osteoporosis, including those from the National Osteoporosis Foundation, and the new fracture risk assessment tool from the World Health Organization. Bisphosphonates are the most commonly used treatment for postmenopausal osteoporosis. Although these agents are effective in preventing fractures and bone loss, the benefits of treatment may be limited by suboptimal adherence and compliance. Denosumab is a human monoclonal antibody that targets and inhibits RANK ligand, an essential mediator of bone resorption. In clinical trials in postmenopausal women with osteoporosis, denosumab 60 mg given subcutaneously every 6 months was well tolerated and statistically significantly reduced the risk of vertebral, nonvertebral, and hip fractures. The introduction of denosumab into clinical practice provides physicians with another option for the treatment of postmenopausal osteoporosis, and the twice-yearly dosing regimen has the potential to improve adherence.     

Osteoporosis in men and women

Osteoporosis is a cause of significant morbidity and mortality in postmenopausal women as well as men. In both men and women, increasing age and low bone mineral density (BMD) are the 2 most important independent risk factors for an initial vertebral or nonvertebral fracture. Although the prevalence of osteoporosis is greater in women, mortality after fracture is higher among men. In both men and women, the incidence of vertebral fracture increases with age, although the increase is more marked in women than in men. The diagnostic criteria for postmenopausal osteoporosis in women are well established; however, there is ongoing debate about the appropriate T-scores and BMD thresholds to diagnose osteoporosis in men. Alendronate and risedronate are considered first-line therapy for the treatment of both postmenopausal osteoporosis and male osteoporosis. The efficacy and safety of these agents have been evaluated extensively in randomized clinical trials. Studies suggest that these agents are similarly efficacious in men and women. The anabolic agent teriparatide may also be used to treat men with osteoporosis at high risk for fracture. Studies suggest that treatment with an anabolic agent like teriparatide should be followed by an antiresorptive agent.     

Pharmacologic prevention of osteoporotic fractures

Osteoporosis is characterized by low bone mineral density and a deterioration in the microarchitecture of bone that increases its susceptibility to fracture. The World Health Organization defines osteoporosis as a bone mineral density that is 2.5 standard deviations or more below the reference mean for healthy, young white women. The prevalence of osteoporosis in black women is one half that in white and Hispanic women. In white women 50 years and older, the risk of osteoporotic fracture is nearly 40 percent over their remaining lifetime. Of the drugs that have been approved for the prevention or treatment of osteoporosis, the bisphosphonates (risedronate and alendronate) are most effective in reducing the risk of vertebral and nonvertebral fractures. Risedronate has been shown to reduce fracture risk within one year in postmenopausal women with osteoporosis and in patients with glucocorticoid-induced osteoporosis. Hormone therapy reduces fracture risk, but the benefits may not outweigh the reported risks. Teriparatide, a recombinant human parathyroid hormone, reduces the risk of new fractures and is indicated for use in patients with severe osteoporosis. Raloxifene has been shown to lower the incidence of vertebral fractures in women with osteoporosis. Salmon calcitonin is reserved for use in patients who cannot tolerate bisphosphonates or hormone therapy.     

Update of current therapeutic options for the treatment of postmenopausal osteoporosis

BACKGROUND: Osteoporosis is a common chronic condition in elderly women and is associated with decreased bone strength and an increased risk for fractures. As the incidence of osteoporotic fractures continues to rise, it is important to identify the most effective therapies for reducing patients' risk of fracture. OBJECTIVE: This article reviews the medication classes commonly used for treating osteoporosis and the efficacy, tolerability, and drug-interaction potential of specific medications. The evidence for the use of combination therapies is summarized, as are the agents under investigation. METHODS: Relevant articles were identified through a search of MEDLINE (August 1985-August 2005) using the terms osteoporosis, postmenopausal, fracture, and efficacy combined with drug therapy, calcium, vitamin D, estrogen, progesterone, selective estrogen modulators, calcitonin, strontium ranelate, bisphosphonates, alendronate, risedronate, ibandronate, pamidronate, parathyroid hormone, combination therapy, and zoledronic acid. The identified articles were reviewed for suitability, with priority given to meta-analyses. RESULTS: Among the therapeutic options for the treatment of osteoporosis, the bisphosphonates appear to provide the greatest antiresorptive efficacy, with some bisphosphonates providing 7% to 8% increases in bone mineral density and 60% to 70% decreases in markers of bone resorption. Bisphosphonates also may reduce the incidence of new vertebral fractures by 50% to 52%. CONCLUSIONS: Bisphosphonates are currently the first choice for the treatment of osteoporosis. Use of intermittent regimens of the newer bisphosphonates appears to be a promising alternative to administration of daily or weekly treatment.     

Management of male osteoporosis: report of the UK Consensus Group

Although osteoporosis is generally regarded as a disease of women, up to 30% of hip fractures and 20% of vertebral fractures occur in men. Risk factors for osteoporotic fractures in men include low body mass index, smoking, high alcohol consumption, corticosteroid therapy, physical inactivity, diseases that predispose to low bone mass, and conditions increasing the risk of falls. The key drugs and diseases that definitely produce a decrease in bone mineral density (BMD) and/or an increase in fracture rate in men are long-term corticosteroid use, hypogonadism, alcoholism and transplantation. Age-related bone loss may be a result of declining renal function, vitamin D deficiency, increased parathyroid hormone levels, low serum testosterone levels, low calcium intake and absorption. Osteoporosis can be diagnosed on the basis of radiological assessments of bone mass, or clinically when it becomes symptomatic. Various biochemical markers have been related to bone loss in healthy and osteoporotic men. Their use as diagnostic tools, however, needs further investigation. A practical approach would be to consider a bone density more than one SD below the age-matched mean value (Z < -1) as an indication for therapy. The treatment options for men with osteoporosis include agents to influence bone resorption or formation and specific therapy for any underlying pathological condition. Testosterone treatment increases BMD in hypogonadal men, and is most effective in those whose epiphyses have not closed completely. Bisphosphonates are the treatment of choice in idiopathic osteoporosis, with sodium fluoride and anabolic steroids to be used as alternatives.      

MiR-26a Rescues Bone Regeneration Deficiency of Mesenchymal Stem Cells Derived From Osteoporotic Mice

Osteoporosis, caused by a relative increase of bone resorption over bone formation, is characterized by decreased bone mass and bone strength, resulting in an increased incidence of bone fractures, which often leads to further disability and early mortality in the elderly due to impaired bone healing ability. The majority of therapeutics currently used in clinics for the treatment of osteoporosis are antiresorptive agents that exert their clinical effect by decreasing the rate of bone resorption. However, strategies solely aimed at antiresorption have limited therapeutic efficacy in restoring bone remodeling balance and enhancing osteoporotic fracture healing. Here, we report that miR-26a plays a critical role in modulating bone formation during osteoporosis. We found that miR-26a treatment could effectively improve the osteogenic differentiation capability of mesenchymal stem cells isolated from littermate-derived ovariectomized osteoporotic mice both in vitro and in vivo. MiR-26a exerts its effect by directly targeting Tob1, the negative regulator of BMP/Smad signaling pathway by binding to the 3′-untranslated region and thus repressing Tob1 protein expression. Our findings indicate that miR-26a may be a promising therapeutic candidate to enhance bone formation in treatment of osteoporosis and to promote bone regeneration in osteoporotic fracture healing.     

Monoclonal antibodies for the treatment of osteoporosis

Introduction: Osteoporosis is a systemic skeletal disorder that weakens bones and increases the risk of fractures. It is caused by perturbations of bone remodeling, the coupled process whereby bone is continually resorbed and formed in small discrete units. Despite the availability of cost-effective pharmacological agents that reduce fracture risk, many patients who could benefit from treatment are not receiving it. Advances in the understanding of the molecular regulators of bone remodeling have led to the identification of new targets for therapeutic intervention. Monoclonal antibodies directed to these targets have recently been developed, providing new ways of modulating bone remodeling that may provide additional benefits beyond previously available therapy.

Areas covered: An approved fully human monoclonal antibody to receptor activator of nuclear factor-κB ligand, the principal regulator of osteoclastic bone resorption, reduces the risk of fractures in postmenopausal women with osteoporosis. Monoclonal antibodies in development include inhibitors of sclerostin and Dickhopf1, with osteoanabolic activity that may be beneficial in the treatment of osteoporosis.

Expert opinion: Monoclonal antibodies to molecular regulators of bone remodeling represent a new class of compounds for the management of osteoporosis and other skeletal disorders associated with an imbalance of bone resorption and formation.     

Osteoporosis in men treated with androgen suppression therapy for prostate cancer

Men with advanced or metastatic prostate cancer commonly receive long-term treatment with luteinizing hormone-releasing hormone (LHRH) agonist therapy. This prolonged treatment causes a hypogonadal state of chronic testosterone deficiency. Similar to estrogen deficiency in postmenopausal women, testosterone deficiency among these men negatively affects bone metabolism through a complex self-regulating, negative feedback system and subsequent reduction in bone formation. If left undetected or untreated, the risk for osteoporosis rises. Osteoporosis increases the likelihood of fracture, especially of the hips. Researchers are studying the effects of LHRH agonist therapy on osteoporosis and other related conditions to determine whether interventions, such as pharmacologic agents (e.g., bisphosphonates), dietary supplements (e.g., calcium, vitamin D), and exercise, can slow or prevent the process and assist healthcare providers in knowing how to counsel patients. Current recommendations are found in the literature on glucocorticoid-induced and menopausal osteoporosis. Nurses need to stay abreast of current knowledge in this area, as it is expanding rapidly.     

骨质疏松症的药物治疗进展

骨质疏松症是一种常见的全身性骨骼疾病,该病的主要特征是骨组织微结构损坏和骨量减少,进而引起骨脆性及骨折风险的增加。随着人口老龄化进程,骨质疏松症的患病率逐年增高,如何防治骨质疏松症已成为全球重要的公共健康问题之一。目前临床上常用的抗骨质疏松症药物主要分为两大类:抑制骨吸收药物和促进骨形成的药物。该文就骨质疏松症的药物治疗进展做一综述。     

Treatment of Postmenopausal Osteoporosis

Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration with a resulting increase in bone fragility and hence susceptibility to fracture. Calcium and vitamin D are the most commonly used therapies for osteoporosis, although their efficacy in osteoporotic fracture prevention remains uncertain. Biphosphonates are the most frequently prescribed medication for treatment of osteoporosis and are often considered as first-line therapy for the treatment of osteoporosis. Currently, hormone replacement therapy is only approved by the Food and Drug Administration (FDA) for short-term treatment of severe postmenopausal symptoms with the lowest dose used for the shortest time. In view of its lack of effect on the prevention of nonvertebral fractures, the use of raloxifene should be limited to women with spinal osteoporosis. Most experts agree that it is preferable to treat osteoporosis with a more potent agent than calcitonin and manage the pain separately. Currently, the FDA recommends the use of parathyroid hormone for treatment of osteoporosis for a maximum of 2 years because of the concern of development of osteosarcoma. Drs. Gupta and Aronow have no real or apparent conflicts of interest relating to the subject under discussion.     

Osteoporosis in premenopause. When are screening and treatment prudent?

Osteoporosis is considered a disorder of postmenopausal women because bone mineral loss and accompanying fragility fractures are common in this group. However, certain premenopausal women are also at risk for osteoporosis. Because of a lack of screening and treatment guidelines for premenopausal women, it can be difficult to determine whether a low bone mineral density correlates with a disease such as osteoporosis and to predict the potential risk of a fracture and formulate the correct course of action. In this article, Dr Derk identifies high-risk groups, presents an approach to judicious screening, and recommends prevention and treatment strategies.     

Osteoporosis--a review

Osteoporosis is a major medical problem in older women. Although a variety of factors influence bone formation and resorption, ovarian failure and a reduction in adrenal androgen production are major causes of menopausal osteoporosis. The prevention of trabecular bone loss and vertebral fractures in menopausal patients is feasible. Women who are at risk, so-called "fast bone losers," can be identified by office and chemical laboratory techniques. Estrogen therapy reduces or halts osteoclastic resorption and preserves bone mass. Exercise and anabolic hormones, including progesterone, stimulate osteoblastic building of bone. The combination of estrogen and progesterone reduces the risk of uterine malignancy below that seen in patients who take estrogen alone and possibly below the incidence seen in women who take no hormones. An individual's doses of replacement hormones will vary, depending on the amount of endogenous bone-targeted hormones and the response to treatment. These doses can be determined by monitoring their effect on 24-hour hydroxyproline and calcium excretion. Another way to monitor dose effect is by observation of the FSH levels. The serum FSH levels should be reduced at least to that level considered to be diagnostic of menopause. It may be unnecessary, if not inappropriate, to strive to restore FSH levels to normal premenopausal levels. Age-associated osteoporosis is a potentially fatal disease. Osteomalacia, with the associated loss of cortical bone, is superimposed upon the trabecular bone loss due to ovarian and adrenal androgen hormone deficiencies. These hormone deficiencies continue to operate upon trabecular bone at this later stage in the continuum. In addition to estrogen therapy and progesterone replacement, patients who are fracture victims may benefit from androgen replacement to increase their bone mass. Replacing androgens using nandrolone decanoate in women may address the natural loss of their adrenal bone-targeted hormones. The identification and treatment of individuals who need vitamin D and calcium replacement will reverse this contribution to the loss of bone. Clinical experience demonstrates that monitored hormone, vitamin D, and calcium supplements reduce the frequency of fractures, especially hip fractures, which may be reduced as much as 40% to 60% over a three-year period with such treatment. Cautious fluoride supplements in addition to calcium, hormones, and appropriate amounts of vitamin D appear to reduce vertebral fracture rates. The associated suffering, disability, and death from osteoporosis-induced fractures can be dramatically altered.(ABSTRACT TRUNCATED AT 400 WORDS)     

Exercise and osteoporosis

Bone formation and resorption are ongoing phenomena. When bone resorption equals bone formation, bone mass remains stable. When resorption exceeds formation, bone mass is reduced--a process that leads to osteopenia or osteoporosis. Osteopenia is reduced bone mass and osteoporosis is reduced bone mass with resultant fractures. Reduced bone mass may be postmenopausal or related to ovarian failure (type I osteoporosis), it may be age-related (type II osteoporosis), or it may result from several other etiologic factors (secondary osteoporosis). Disuse and inactivity can cause bone loss, whereas weight-bearing exercises may maintain or improve bone mineral density. There is a significant correlation between muscle strength and bone mineral density. There is evidence that strengthening exercises may lead to an increase in the mineral density of the bones to which the muscles are attached. Currently, drug regimens are available to decrease or halt bone loss in osteoporotic patients. Properly designed exercise programs may prove to be effective for retarding age-related bone loss. In patients with osteoporosis, the cause should be investigated before treatment is commenced.     

中药治疗骨质疏松症研究进展

骨质疏松是由多种原因引起的一组骨病,以骨量减少、骨密度降低、易发骨折为特征。近年来中药对骨质疏松治疗方面的研究日益增多,不少中药具有促进骨形成、抑制骨吸收的作用,被应用于防治骨质疏松,取得初步疗效。本文就目前治疗骨质疏松症的中药常用单药及方剂的疗效及作用机制进行简要综述,为临床研究提供参考。     

Epidemiology of fractures and assessment of fracture risk

Osteoporosis is a common condition that is clinically important because of its association with fracture. Fracture risk is ultimately determined by the relation between bone strength and propensity to trauma. Bone density is a key determinant of bone strength, and depends on the bone gained during growth and consolidation, and the subsequent rate of bone loss. Many factors (both genetic and environmental) influence the risk of future fracture through effects on these key intermediary mechanisms. Fracture risk increases greatly with age and is generally higher in women than in men and in whites than in other races. Around 30% to 40% of the variance in peak bone mass is genetically determined, and polymorphisms for several candidate genes are currently being identified. Sex hormone deficiency after the menopause is a key factor in the pathogenesis of osteoporosis in women. In addition, however, there are environmental influences that affect bone density, such as cigarette smoking, alcohol consumption, physical inactivity, and nutrition. Using age, BMD, and other risk factors, it is now possible to identify populations at high risk of osteoporotic fractures. Such populations will potentially derive maximal benefit from therapies and other strategies that reduce fracture risk.     

Risedronate for the prevention of fractures in postmenopausal osteoporosis

OBJECTIVE: To evaluate current scientific literature regarding the efficacy of risedronate in the prevention of vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. DATA SOURCES: Primary research articles were identified by MEDLINE search (1966-May 2001) and through secondary sources. Key search terms were risedronate, postmenopausal osteoporosis, and fractures. DATA SYNTHESIS: Osteoporosis results in a reduction of bone mineral density, increased bone fragility, and increased risk of fractures. The goal of osteoporosis therapy is not only to increase bone mass, but also to reduce the rate of fractures. Risedronate is the newest bisphosphonate to be approved for the prevention and treatment of osteoporosis. An evaluation of clinical trials using risedronate in the treatment of postmenopausal osteoporosis was performed to determine its efficacy at decreasing fracture rates. CONCLUSIONS: Risedronate is an effective and safe option for the treatment of postmenopausal osteoporosis. Risedronate significantly decreases the risk of vertebral and nonvertebral fractures in women who have had > or =1 fractures in the past. More studies are warranted to evaluate the efficacy of risedronate in women without preexisting vertebral fractures.