Osteoporosis: Bilezikian JP

Lewiecki EM, Baim S, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S, Anonymous00044. · New Mexico Clinical Research and Osteoporosis Center, Albuquerque, NM 87106, USA. · South Med J. · Pubmed #18580720 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) periodically holds Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines for the assessment of skeletal health -- the nomenclature, indications, acquisition, analysis, quality control, interpretation, and reporting of bone density tests. Topics are selected for consideration according to criteria that include clinical relevancy, uncertainty in the application of medical evidence to clinical practice, and the likelihood of the expert panel achieving agreement. The most recent Adult PDC was held July 20 to 22, 2007, in Lansdowne, Virginia. Topics included technical and clinical issues relevant to dual-energy x-ray absorptiometry (DXA), vertebral fracture assessment, and bone densitometry technologies other than central DXA. This report describes the methodology and presents the results of this PDC. The first ISCD Pediatric PDC was held June 20 to 21, 2007 in Montreal, Quebec, Canada, and is reported separately.

Khan AA, Hanley DA, Bilezikian JP, Binkley N, Brown JP, Hodsman AB, Josse RG, Kendler DL, Lewiecki EM, Miller PD, Olszynski WP, Petak SM, Syed ZA, Theriault D, Watts NB, Anonymous00369. · Division of Endocrinology, McMaster University, Hamilton, Ontario, Canada, and Hanover General Hospital, PA, USA. · J Clin Densitom. · Pubmed #16731431 No free full text.

Abstract: This document addresses skeletal health assessment in individuals with secondary causes of osteoporosis. Recommendations are based on consensus of the Canadian Panel of the International Society for Clinical Densitometry and invited international experts. Bone mineral density (BMD) testing in these populations is performed in conjunction with careful evaluation of the disease state contributing to bone loss and increased fragility fracture risk, as well as assessment of other contributing risk factors for fracture. The presence of secondary causes of bone loss may further increase the risk of fracture independently of BMD and may necessitate earlier pharmacologic intervention. Dual-energy X-ray absorptiometry is indicated in the initial workup of secondary causes of osteoporosis. The BMD fracture risk relationship is not known for individuals with chronic renal failure (CRF). The BMD testing in this population may be normal in the presence of skeletal fragility, and quantitative bone histomorphometry is better at evaluating skeletal status than BMD in CRF. Dual-energy X-ray absorptiometry is a valuable tool in assessing skeletal health in individuals with secondary causes of osteoporosis.

Binkley N, Bilezikian JP, Kendler DL, Leib ES, Lewiecki EM, Petak SM, Anonymous00364. · University of Wisconsin, Madison, WI, USA. · J Clin Densitom. · Pubmed #16731426 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) convenes a Position Development Conference (PDC) every two years for the purpose of making recommendations on clinically relevant issues in bone densitometry. Topics for consideration are developed by the ISCD Scientific Advisory Committee and the PDC Steering Committee. Clinically relevant questions related to each topic area are assigned to subcommittees for a comprehensive medical literature review and presentation of a report to an international panel of experts. The expert panel includes representatives of the American Society for Bone and Mineral Research (ASBMR) and the International Osteoporosis Foundation (IOF). The recommendations of the PDC expert panel are evaluated by the ISCD Board of Directors, and those that are approved become Official Positions of the ISCD. The Official Positions have subsequently been endorsed by the ASBMR and IOF. The most recent PDC was held July 15-17, 2005, in Vancouver, BC, Canada. Topics considered included technical standardization, vertebral fracture assessment, and application of the 1994 World Health Organization (WHO) criteria to various skeletal sites and to populations other than postmenopausal white women. This report describes the methodology of the 2005 PDC and presents a summary of all ISCD Official Positions.

Hodgson SF, Watts NB, Bilezikian JP, Clarke BL, Gray TK, Harris DW, Johnston CC, Kleerekoper M, Lindsay R, Luckey MM, McClung MR, Nankin HR, Petak SM, Recker RR, Anonymous00007. · No affiliation provided · Endocr Pract. · Pubmed #14715483 No free full text.

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Ettinger B, Bilezikian JP. · No affiliation provided · J Clin Endocrinol Metab. · Pubmed #11889148 links to  free full text

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Rosen CJ, Bilezikian JP. · No affiliation provided · J Clin Endocrinol Metab. · Pubmed #10599703 links to  free full text

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Bilezikian JP. · Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. · Am J Med. · Pubmed #19187808 No free full text.

Abstract: Bisphosphonates have been available for more than a decade. Currently, 4 bisphosphonates--alendronate, risedronate, ibandronate, and zoledronic acid--are approved in the United States. Alendronate and risedronate are oral agents, ibandronate is available in oral and intravenous formulations, and zoledronic acid is an intravenous drug. This review summarizes results from pivotal clinical trials in which these bisphosphonates have been shown to reduce risk for osteoporotic fractures. Also reviewed are results of "bridging" studies designed to demonstrate the comparable efficacy of less frequent dosing regimens to increase bone mineral density and to reduce bone turnover. Compared with placebo controls, all 4 approved bisphosphonates reduce the relative risk of new vertebral fractures in women with postmenopausal osteoporosis. Alendronate, risedronate, and zoledronic acid reduce the relative risk of new nonvertebral and hip fractures. Clinical trial extensions of up to 10 years with alendronate and 7 years with risedronate have shown that efficacy is maintained during long-term treatment.

Doga M, Mazziotti G, Bonadonna S, Patelli I, Bilezikian JP, Canalis E, Giustina A. · Department of Internal Medicine, University of Brescia, Brescia, Italy. · J Endocrinol Invest. · Pubmed #18791353 No free full text.

Abstract: Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis with fractures occurring in as many as 30-50% of patients receiving chronic glucocorticoid therapy. Calcium and vitamin D are important measures in the primary prevention of GIO. However, vitamin D and calcium alone do not allow to prevent fractures. Estrogens and androgens should be used in patients with documented hypogonadism. Bisphosphonates are the most effective of the various therapies that have been assessed for the management of GIO. These drugs need to be started early in order to correct the increase in bone resorption occurring in the first weeks of glucocorticoid treatment. Anabolic therapeutic strategies are under investigation. Teriparatide seems to be also efficacious for the treatment of patients with GIO.

Walker MD, Novotny R, Bilezikian JP, Weaver CM. · Division of Endocrinology, Metabolic Bone Disease Unit, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. · J Nutr. · Pubmed #18492866 links to  free full text

Abstract: Racial differences in bone become apparent during puberty. Studies of areal bone mineral density (aBMD) generally show the greatest aBMD in African Americans followed by American white, Hispanic, and Native Americans, with the least aBMD in Asian Americans. Racial differences in fracture risk, however, do not exactly follow racial variation in aBMD. These group differences in bone mass are largely explained by differences in bone size, although calcium intake and physical activity are also significant predictors of aBMD and bone mineral content. Racial differences in calcium metabolism, as influenced by calcium and sodium intake, explain much of the black vs. white differences in skeletal calcium accretion during puberty. The relative importance of calcium and sodium in calcium metabolism has not yet been elucidated among Asians. Predictors of aBMD have been reported for African American and American white adults and predictors of aBMD in Chinese American women have recently been studied. Much remains to be studied regarding interactions between race and diet.

Bilezikian JP. · Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.E-mail: · Curr Osteoporos Rep. · Pubmed #18430397 No free full text.

Abstract: Antiresorptive agents for osteoporosis are a cornerstone of therapy, but anabolic drugs have recently increased our options. By stimulating bone formation, anabolic agents reduce fracture incidence by improving bone qualities in addition to increasing bone mass. The only anabolic agent currently approved for osteoporosis by the US Food and Drug Administration, teriparatide (recombinant human parathyroid hormone ), has emerged as a major approach to selected patients with osteoporosis. Recombinant human parathyroid hormone (1-84) is also available in Europe. Teriparatide increases bone density and bone turnover, improves microarchitecture, and changes bone size. The incidence of vertebral and nonvertebral fractures is reduced. A current concept in the mechanism of teriparatide action is related to its effect to stimulate processes associated with bone formation before it stimulates processes associated with bone resorption. This sequence of events has led to the concept of the anabolic window, the period of time when teriparatide is maximally anabolic. Newer approaches to the use of teriparatide alone and in combination with antiresorptive agents have led to ways in which the anabolic window can be expanded.

Mazziotti G, Giustina A, Canalis E, Bilezikian JP. · Department of Internal Medicine, University of Brescia, Italy. · Arq Bras Endocrinol Metabol. · Pubmed #18209880 links to  free full text

Abstract: Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis. Fractures, which are often asymptomatic, may occur in as many as 30-50% of patients receiving chronic glucocorticoid therapy. Vertebral fractures occur early after exposure to glucocorticoids, at a time when bone mineral density (BMD) declines rapidly. Fractures tend to occur at higher BMD levels than in women with postmenopausal osteoporosis. Glucocorticoids have direct and indirect effects on the skeleton. They impair the replication, differentiation, and function of osteoblasts and induce the apoptosis of mature osteoblasts and osteocytes. These effects lead to a suppression of bone formation, a central feature in the pathogenesis of GIO. Glucocorticoids also favor osteoclastogenesis and as a consequence increase bone resorption. Bisphosphonates are the most effective of the various therapies that have been assessed for the management of GIO. Anabolic therapeutic strategies are under investigation. Teriparatide seems to be also efficacious for the treatment of patients with GIO.

Canalis E, Giustina A, Bilezikian JP. · Department of Research, Saint Francis Hospital and Medical Center, Hartford, CT 06105-1299, USA. · N Engl J Med. · Pubmed #17761594 No free full text.

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Canalis E, Mazziotti G, Giustina A, Bilezikian JP. · Saint Francis Hospital and Medical Center, Hartford, CT 060105, USA. · Osteoporos Int. · Pubmed #17566815 No free full text.

Abstract: Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis. Fractures, which are often asymptomatic, may occur in as many as 30-50% of patients receiving chronic glucocorticoid therapy. Vertebral fractures occur early after exposure to glucocorticoids, at a time when bone mineral density (BMD) declines rapidly. Fractures tend to occur at higher BMD levels than in women with postmenopausal osteoporosis. In human subjects, the early rapid decline in BMD is followed by a slower progressive decline in BMD. Glucocorticoids have direct and indirect effects on the skeleton. The primary effects are on osteoblasts and osteocytes. Glucocorticoids impair the replication, differentiation and function of osteoblasts and induce the apoptosis of mature osteoblasts and osteocytes. These effects lead to a suppression of bone formation, a central feature in the pathogenesis of GIO. Glucocorticoids also favor osteoclastogenesis and as a consequence increase bone resorption. Bisphosphonates are effective in the prevention and treatment of GIO. Anabolic therapeutic strategies are under investigation.

Gennari L, Bilezikian JP. · Department of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena 53100, Italy. · Endocrinol Metab Clin North Am. · Pubmed #17543726 No free full text.

Abstract: Osteoporosis has long been considered to be a disease of the aging female skeleton. As awareness of the pervasiveness of this disorder increases, it is clear that men are also at risk for this disorder. Recent epidemiological studies have confirmed that osteoporosis in men is an increasing health problem. This development not only has its roots in increased longevity but also in increased awareness of this problem in men. The purpose of this article is to review what is known about the factors in men that lead to acquisition, maintenance, and loss of bone, as well as new insights about the causes, pathogenesis, and treatment of osteoporosis in men.

Gennari L, Bilezikian JP. · College of Physicians and Surgeons, 630 W. 168th Street, New York, NY 10032, USA. · Curr Rheumatol Rep. · Pubmed #17437671 No free full text.

Abstract: Osteoporosis has long been long considered a disease of the aging female skeleton. However, it is now clear that men are also at risk for this disorder. Epidemiologic studies have confirmed that osteoporotic fractures in men are an increasing public health problem, in part due to increased longevity and increased public awareness. Recent large-scale population studies in men have led to advances in our understanding of bone fragility and its treatment in men. This article reviews what is known about the factors in men that lead to acquisition, maintenance, and loss of bone, as well as new insights into causes, pathogenesis, and treatment of osteoporosis in men.

Borges JL, Bilezikian JP. · Universidade Catolica de Brasilia, DF, Brazil. · Arq Bras Endocrinol Metabol. · Pubmed #17117300 links to  free full text

Abstract: Osteoporosis is a skeletal disorder characterized by compromised bone strength that predisposes a person to increased fracture risk. Fractures are often associated with increased morbidity, higher mortality, loss of function and even psychological consequences. Pharmacotherapeutic interventions (e.g., bisphosphonates, selective estrogen receptor modulators, calcitonin, and teriparatide) in women with postmenopausal osteoporosis provide substantial reduction in fracture risk over and above risk reduction with calcium and vitamin D supplementation alone. The importance of nutritional support along with an appropriate exercise regimen, avoiding smoking and excessive alcohol use is to be emphasized along with the pharmacologic approach to osteoporosis. Despite the effectiveness of therapy with pharmacologic agents, most patients who start therapy do not remain on treatment for more than 1 year.

Girotra M, Rubin MR, Bilezikian JP. · Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. · Arq Bras Endocrinol Metabol. · Pubmed #17117299 links to  free full text

Abstract: Antiresorptive agents for osteoporosis are a cornerstone of therapy, but anabolic drugs have recently widened our therapeutic options. By directly stimulating bone formation, anabolic agents reduce fracture incidence by improving bone qualities besides increasing bone mass. In this article, we review the role of anabolic treatment for osteoporosis. The only anabolic agent currently approved in the United States for osteoporosis, teriparatide [recombinant human parathyroid hormone(1-34)], has clearly emerged as a major approach to selected patients with osteoporosis. Teriparatide increases bone density and bone turnover, improves microarchitecture, and changes bone size. The incidence of vertebral and nonvertebral fractures is reduced. Teriparatide is approved for both postmenopausal women and men with osteoporosis who are at high risk for fracture. Other potential anabolic therapies for osteoporosis, including other forms of parathyroid hormone, strontium ranelate, growth hormone, and insulin-like growth factor-1, are also reviewed in this article.

Girotra M, Rubin MR, Bilezikian JP. · Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, New York, NY 10032, USA. · Rev Endocr Metab Disord. · Pubmed #17043762 No free full text.

Abstract: Anabolic skeletal agents have recently broadened our therapeutic options for osteoporosis. By directly stimulating bone formation, they reduce fracture incidence by improving bone qualities in addition to increasing bone mass. Teriparatide [recombinant human parathyroid hormone(1-34)], the only anabolic agent currently approved in the United States for osteoporosis, has emerged as a major therapeutic approach to selected patients with osteoporosis. Teriparatide is approved for both postmenopausal women and men with osteoporosis who are at high risk for fracture. With the use of this anabolic agent, bone density and bone turnover increase, microarchitecture improves, and bone size is beneficially altered. The incidence of vertebral and nonvertebral fractures is reduced with teriparatide use. Combination therapy with parathyroid hormone and an antiresorptive does not appear to offer definitive advantages over the use of PTH or an antiresorptive alone, although recent ideas about combining these agents may offer new insights. In order to maintain increases in bone density acquired during PTH therapy, it is important to follow its use with an antiresorptive agent.

Mazziotti G, Angeli A, Bilezikian JP, Canalis E, Giustina A. · Department of Internal Medicine, Spedali Civili, University of Brescia, 25125 Brescia, Italy. · Trends Endocrinol Metab. · Pubmed #16678739 No free full text.

Abstract: Glucocorticoid-induced osteoporosis occurs in two phases: a rapid, early phase in which bone mineral density is reduced, possibly as a result of excessive bone resorption, and a slower, progressive phase in which bone mineral density declines because of impaired bone formation. Although the indirect effects of glucocorticoids on bone are evident, their direct effects on osteoblasts, osteoclasts and osteocytes are primarily operative in the pathogenesis of glucocorticoid-induced osteoporosis. The management of patients exposed to glucocorticoids includes general health measures, sufficient calcium and vitamin D, and reducing the therapeutic regimen to the minimal effective dose. The gold standard in the pharmacological treatment of glucocorticoid-induced osteoporosis in postmenopausal women involves the use of bisphosphonates, which should be started soon after beginning chronic glucocorticoid therapy. Anabolic and alternative therapeutic strategies are currently under investigation in glucocorticoid-induced osteoporosis.

Bilezikian JP, Rubin MR. · Department of Medicine, College of Physicians and Surgeons, New York, NY 10032, USA. · Curr Osteoporos Rep. · Pubmed #16527002 No free full text.

Abstract: In this paper, we focus upon the use of anabolic skeletal therapy for the treatment of postmenopausal and other forms of osteoporosis. The only anabolic skeletal agent currently available is a recombinant bioactive fragment of parathyroid hormone, PTH(1-34), known as teriparatide. The full length molecule, human PTH(1-84) is being investigated at this time as are other PTH molecules. Teriparatide improves bone quality by actions on bone turnover, bone density, bone size, and microarchitecture. In postmenopausal women with osteoporosis, teriparatide reduces the incidence for vertebral and nonvertebral fractures. In individuals who have been treated previously with an antiresorptive agent, the subsequent actions of teriparatide on bone density are delayed transiently if bone turnover is markedly suppressed. Combination therapy with teriparatide or PTH(1-84) and an antiresorptive does not appear, at this time, to offer advantages over the use of PTH or an antiresorptive alone. To maintain the gains in bone density with PTH, it is important to follow its use with an antiresorptive agent.

Bilezikian JP. · Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. · Int J Fertil Womens Med. · Pubmed #16334411 No free full text.

Abstract: Until recently, calcium supplementation with vitamin D and hormone replacement therapy were the mainstays of treating osteoporosis associated with the menopause. Hormone replacement therapy, indeed, was (and is) effective in preventing fracture, but is no longer to be considered to be a primary indication for this purpose. Thus, while continuing with calcium and vitamin D, drug therapy now consists of the antiresorptive agents: raloxifene, calcitonin, and the bisphosphonates. These drugs reduce bone turnover, and do prevent fractures, but are limited to halting further deterioration of skeletal microarchitecture. The newest agent against osteoporosis is teriparatide, an amino terminal fragment parathyroid hormone containing 34 amino acids. PTH(1-34), or teriparatide, exhibits many of the classical actions of the whole molecule. It is anabolic with respect to bone when used according to well-defined protocols. Bone microarchitecture is restored with increases in cortical thickness and in connectivity. This paper describes the activities as known at present of the bisphosphonates and of teriparatide and reviews studies of their use alone and in combination with each other.

Bilezikian JP, Rubin MR, Finkelstein JS. · Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. · J Endocrinol Invest. · Pubmed #16329201 No free full text.

Abstract: The quest for effective treatment of osteoporosis merits great attention because of the widespread, worldwide prevalence of this disease. Antiresorptive drugs reduce bone turnover, increase bone density and improve other aspects of bone quality. This article concentrates on another approach, namely the use of anabolic therapy in which the prospects for improving bone quality are even greater. Parathyroid hormone is available as the aminoterminal fragment, PTH(1-34), known as teriparatide, and is being studied in its full-length form, PTH(1-84). Teriparatide improves bone quality by actions on bone turnover, bone density, bone size and microarchitecture. In women, teriparatide reduces both vertebral and non-vertebral fractures. In individuals who have been treated previously with an antiresorptive agent, the ability of PTH to increase bone density may be reduced. Combination therapy with teriparatide or PTH(1-84) and an antiresorptive does not appear, at this time, to offer advantages over the use of parathyroid hormone alone. In order to maintain the densitometric gains in bone density with parathyroid hormone, it is important to follow its use with an antiresorptive agent.

Rubin MR, Bilezikian JP. · Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. · Drugs. · Pubmed #16296873 No free full text.

Abstract: The quest for effective treatment for osteoporosis merits great attention because of the widespread prevalence of this disease, which is not only associated with fragility fractures, but also with significant morbidity and mortality. The efficacy of the antiresorptive drugs in this disease is achieved by reducing bone turnover, increasing bone density and improving other aspects of bone quality. This article concentrates on another approach to the treatment of osteoporosis, namely the use of anabolic therapy, which has even greater prospects for improving bone quality.Parathyroid hormone (PTH) is currently available only as the recombinant amino-terminal fragment, PTH(1-34), known as teriparatide. The full-length molecule, human PTH(1-84), is currently being investigated, as are other PTH molecules. Teriparatide improves bone quality through actions on bone turnover, bone density, bone size and bone microarchitecture. In postmenopausal women with osteoporosis, teriparatide reduces the incidence of vertebral and nonvertebral fractures. In individuals who have previously been treated with an antiresorptive agent, the subsequent actions of teriparatide on bone density are transiently delayed if bone turnover has been markedly suppressed. Combination therapy with teriparatide or PTH(1-84) and an antiresorptive agent does not appear, at this time, to offer advantages over the use of PTH or an antiresorptive agent alone. However, in order to maintain the densitometric gains in bone density obtained with PTH, it is important to follow its use with that of an antiresorptive agent.

Canalis E, Bilezikian JP, Angeli A, Giustina A. · Saint Francis Hospital and Medical Center, Hartford, CT 06105, USA. · Bone. · Pubmed #15050888 No free full text.

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Bilezikian JP. · No affiliation provided · Osteoporos Int. · Pubmed #14504715 No free full text.

Abstract: In primary hyperparathyroidism, as is the case for any metabolic bone disease like osteoporosis, bone strength is a function of many variables. In addition to bone density, considerations of bone size, microarchitecture, and dynamic variables related to the evolution of the disease are all likely to influence bone strength. With greater tools to investigate these points and with newly identified cohorts of this disease, some of whom are presenting with the earliest manifestations of abnormal parathyroid function, it is expected that fresh insights will emerge. Greater knowledge of the disease should help in understanding anabolic aspects of PTH when it is used as a treatment for osteoporosis.