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Michael R McClung
Romosozumab, a specific inhibitor of sclerostin, is a unique approach to therapy for postmenopausal osteoporosis and related disorders. The elucidation of sclerostin deficiency as the molecular defect of syndromes of high bone mass with normal quality, and the pivotal role of sclerostin as a mediator of osteoblastic activity and bone formation, provided the platform for the evaluation of inhibitors of sclerostin to activate bone formation. An extensive preclinical program and 2 large fracture endpoint trials with romosozumab, a sclerostin-binding antibody, have been completed...
March 2018: Osteoporosis and Sarcopenia
Massimo Marenzana, Timothy R Arnett
The importance of the vascular supply for bone is well-known to orthopaedists but is still rather overlooked within the wider field of skeletal research. Blood supplies oxygen, nutrients and regulatory factors to tissues, as well as removing metabolic waste products such as carbon dioxide and acid. Bone receives up to about 10% of cardiac output, and this blood supply permits a much higher degree of cellularity, remodelling and repair than is possible in cartilage, which is avascular. The blood supply to bone is delivered to the endosteal cavity by nutrient arteries, then flows through marrow sinusoids before exiting via numerous small vessels that ramify through the cortex...
September 2013: Bone Research
Mattias Lorentzon
Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications. These drugs increase bone mineral density (BMD) and reduce the risk of vertebral (by 40-70%), nonvertebral (by 25-40%) and hip fractures (by 40-53%) in postmenopausal women with osteoporosis. Due to the risk of rare side-effects, the use of bisphosphonates has been limited to up to 10 years with oral bisphosphonates and 6 years with intravenous zoledronic acid. Despite their well-proven efficacy and safety, few women at high risk of fracture are started on treatment...
January 18, 2019: Journal of Internal Medicine
Jesse Zanker, Gustavo Duque
Osteoporosis is the most common bone disease in humans. Older persons are at higher risk of osteoporotic fractures that also result in poor quality of life, disability, loss of independence, institutionalization, and higher mortality. Osteoporosis shares a distinct pathophysiologic relationship with sarcopenia, an age-related disease comprising declines in muscle mass, strength, or function. The combination of these two diseases is known as osteosarcopenia. Understanding the pathophysiology of osteosarcopenia, in addition to its diagnostic and therapeutic approaches, is key in providing older adults with the best falls and fractures prevention strategies...
December 20, 2018: Journal of the American Geriatrics Society
Gill Holdsworth, Scott J Roberts, Hua Zhu Ke
The discovery that two rare autosomal recessive high bone mass conditions were caused by the loss of sclerostin expression prompted studies into its role in bone homeostasis. In this article, we aim to bring together the wealth of information relating to sclerostin in bone though discussion of rare human disorders in which sclerostin is reduced or absent, sclerostin manipulation via genetic approaches and treatment with antibodies that neutralise sclerostin in animal models and in human. Together, these findings demonstrate the importance of sclerostin as a regulator of bone homeostasis and provide valuable insights into its biological mechanism of action...
February 1, 2019: Journal of Molecular Endocrinology
Houchen Lyu, Bakr Jundi, Chang Xu, Sara K Tedeschi, Kazuki Yoshida, Sizheng Zhao, Sagar U Nigwekar, Benjamin Z Leder, Daniel H Solomon
Background: Among the currently available osteoporosis therapeutics, bisphosphonates and denosumab are widely used. However, it remains uncertain which therapy is more effective. Objective: To determine whether the use of denosumab increases bone mineral density (BMD) and reduces the risk of fractures more than bisphosphonates in patients with low BMD or osteoporosis. Data Sources: We searched PubMed, Embase and the Cochrane Library through Nov 2018...
December 10, 2018: Journal of Clinical Endocrinology and Metabolism
Francesca Sassi, Cristina Tamone, Patrizia D'Amelio
The classical functions of vitamin D are to regulate calcium-phosphorus homeostasis and control bone metabolism. However, vitamin D deficiency has been reported in several chronic conditions associated with increased inflammation and deregulation of the immune system, such as diabetes, asthma, and rheumatoid arthritis. These observations, together with experimental studies, suggest a critical role for vitamin D in the modulation of immune function. This leads to the hypothesis of a disease-specific alteration of vitamin D metabolism and reinforces the role of vitamin D in maintaining a healthy immune system...
November 3, 2018: Nutrients
Ilse Yessabel Martinez Munoz, Eneida Del Socorro Camarillo Romero, Jose de Jesus Garduno Garcia
The rising prevalence of chronic diseases such as type 2 diabetes and cardiovascular diseases owing to fat mass excess has been described. In recent years, muscle function/dysfunction has become relevant in metabolic homeostasis. Irisin was described as an exercise-induced myokine. It is the product of type I membrane protein cleavage encoded by the fibronectin type III domain containing 5 (FNDC5) gene. The main beneficial function attributable to irisin is the change of subcutaneous and visceral adipose tissue into brown adipose tissue, with a consequential increase in thermogenesis...
2018: International Journal of Endocrinology
Lynda Bonewald
Until recently, it was assumed that the only interaction between muscle and bone is mechanical, that the muscle acts as a pulley and the bone as a lever to move the organism. A relatively new concept is that muscle, especially contracted muscle, acts as a secretory organ, regulating metabolism. An even newer concept is that bone, especially the osteocytes in bone, act as endocrine cells targeting other organs such as kidney and more recently, muscle. These two new concepts logically led to the third concept: that muscle and bone communicate via soluble factors...
March 2019: Bone
Clifford J Rosen
New England Journal of Medicine, Volume 379, Issue 25, Page 2465-2466, December 2018.
December 20, 2018: New England Journal of Medicine
Sabashini K Ramchand, Ego Seeman
The prevalence of fragility fractures increases as longevity increases the proportion of the elderly in the community. Until recently, the majority of studies have targeted women with osteoporosis defined as a bone mineral density (BMD) T score of < -2.5 SD, despite evidence that the population burden of fractures arises from women with osteopenia. Antiresorptive agents reduce vertebral and hip fracture risk by ~50 percent during 3 years but efficacy against non-vertebral fractures, 80% of all fractures in the community, is reported in few studies, and of those, the risk reduction is only 20-30%...
2018: Frontiers in Endocrinology
Andrea V Haas, Meryl S LeBoff
Medications for osteoporosis are classified as either antiresorptive or anabolic. Whereas antiresorptive agents prevent bone resorption, anabolic agents promote new bone formation. Anabolics should be considered in individuals with severe osteoporosis, failure of alternative osteoporosis agents, intolerability or contraindications to other osteoporosis agents, and glucocorticoid-induced osteoporosis. There are currently two approved anabolic therapies, teriparatide and abaloparatide, and a third anabolic agent, romozosumab, is under review by the US Food and Drug Administration...
August 1, 2018: Journal of the Endocrine Society
John P Bilezikian
Background: Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women. The clinical presentation of PHPT has evolved over the past 40 years to include three distinct clinical phenotypes, each of which has been studied in detail and has led to evolving concepts about target organ involvement, natural history, and management. Methods: In the present review, I provide an evidence-based summary of this disorder as it has been studied worldwide, citing key concepts and data that have helped to shape our concepts about this disease...
November 1, 2018: Journal of Clinical Endocrinology and Metabolism
Sakiko Soutome, Saki Hayashida, Madoka Funahara, Yuki Sakamoto, Yuka Kojima, Souichi Yanamoto, Masahiro Umeda
Methods for preventing medication-related osteonecrosis of the jaw (MRONJ) in cancer patients who have received high-dose bisphosphonate (BP) or denosumab (Dmab) have not yet been established. Tooth extraction after starting medication has been believed to be a major risk factor for MRONJ, and therefore this procedure tends to be avoided. This study investigated the risk factors for MRONJ, with a special reference to the correlation between tooth extraction and development of MRONJ. One hundred and thirty-five cancer patients who were administrated high-dose BP or Dmab were enrolled in the study...
2018: PloS One
Amy Jennings, Kevin D Cashman, Rachel Gillings, Aedin Cassidy, Jonathan Tang, William Fraser, Kirsten G Dowling, George L J Hull, Agnes A M Berendsen, Lisette C P G M de Groot, Barbara Pietruszka, Elzbieta Wierzbicka, Rita Ostan, Alberto Bazzocchi, Giuseppe Battista, Elodie Caumon, Nathalie Meunier, Corinne Malpuech-Brugère, Claudio Franceschi, Aurelia Santoro, Susan J Fairweather-Tait
Background: The Mediterranean diet (MD) is widely recommended for the prevention of chronic disease, but evidence for a beneficial effect on bone health is lacking. Objective: The aim of this study was to examine the effect of a Mediterranean-like dietary pattern [NU-AGE (New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe)] on indexes of inflammation with a number of secondary endpoints, including bone mineral density (BMD) and biomarkers of bone and collagen degradation in a 1-y multicenter randomized controlled trial (RCT; NU-AGE) in elderly Europeans...
September 1, 2018: American Journal of Clinical Nutrition
Jessica Starr, Yu Kwang Donovan Tay, Elizabeth Shane
PURPOSE OF REVIEW: To summarize reports published since the 2013 American Society of Bone and Mineral Research Task Force Report on atypical femoral fractures (AFF). RECENT FINDINGS: The absolute incidence of AFFs remains low. AFFs are primarily associated with prolonged bisphosphonate (BP) exposure, but have also been reported in unexposed patients and those receiving denosumab for osteoporosis and metastatic bone disease. Asians may be more susceptible to AFFs...
August 2018: Current Osteoporosis Reports
E Michael Lewiecki, Tomasz Blicharski, Stefan Goemaere, Kurt Lippuner, Paul D Meisner, Paul D Miller, Akimitsu Miyauchi, Judy Maddox, Li Chen, Stephane Horlait
Context: Globally, one in five men aged >50 years is predicted to experience an osteoporotic fracture. Because of the treatment gap in osteoporosis and the paucity of bone-forming agents for men, new osteoporosis treatments are needed. Objective: To evaluate the safety and efficacy of romosozumab in men with osteoporosis. Design: Phase III randomized BRIDGE study (placebo-controlled double-blind study evaluating the efficacy and safety of romosozumab in treating men with osteoporosis; ClinicalTrials...
September 1, 2018: Journal of Clinical Endocrinology and Metabolism
Lynda Frassetto, Tanushree Banerjee, Neil Powe, Anthony Sebastian
Modern Western diets, with higher contents of animal compared to fruits and vegetable products, have a greater content of acid precursors vs. base precursors, which results in a net acid load to the body. To prevent inexorable accumulation of acid in the body and progressively increasing degrees of metabolic acidosis, the body has multiple systems to buffer and titrate acid, including bone which contains large quantities of alkaline salts of calcium. Both in vitro and in vivo studies in animals and humans suggest that bone base helps neutralize part of the dietary net acid load...
April 21, 2018: Nutrients
Mikio Kamimura, Akira Taguchi, Yukio Nakamura, Hidefumi Koiwai, Shota Ikegami, Shigeharu Uchiyama, Hiroyuki Kato
Background: While it is well known that teriparatide (TPTD) increases bone mineral density (BMD) in osteoporotic patients, it is unknown whether TPTD pretreatment affects BMD after denosumab (DMAb) therapy. Methods: Fifty-seven patients in TPTD-pretreated group and 35 patients in DMAb-alone group had been further analyzed, all of whom were treated by DMAb for 1.5 years. Vitamin D (400 IU) and Ca (600 mg) supplementation was used in all patients. The BMD of lumbar 1-4 vertebrae (L-BMD), bilateral total hips (H-BMD), and bilateral femoral neck (FN-BMD) was quantified at first visit, and at 4, 8, 12, and 18 months after daily TPTD treatment following four times DMAb treatment...
2018: Therapeutics and Clinical Risk Management
Felicia Cosman, Daria B Crittenden, Serge Ferrari, Aliya Khan, Nancy E Lane, Kurt Lippuner, Toshio Matsumoto, Cassandra E Milmont, Cesar Libanati, Andreas Grauer
Romosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption. In FRActure study in postmenopausal woMen with ostEoporosis (FRAME), postmenopausal women with osteoporosis received romosozumab 210 mg s.c. or placebo once monthly for 12 months, followed by denosumab 60 mg s.c. once every 6 months in both groups for 12 months. One year of romosozumab increased spine and hip BMD by 13% and 7%, respectively, and reduced vertebral and clinical fractures with persistent fracture risk reduction upon transition to denosumab over 24 months...
July 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
2018-03-26 12:57:42
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