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Carolina A Moreira, John P Bilezikian
CONTEXT: Stress fractures are repetitive use injuries in which recurrent strains lead to material fatigue and microarchitectural discontinuities. Stress fractures account for up to 20% of athletic injuries, more commonly sustained by women and in those who engage in track-and-field events. The pathogenesis of stress fractures is multifactorial. Although most stress fracture are reported among women who may experience menstrual disturbances, low body mass index, low energy intake and sometimes low bone mass, these individuals do not regularly seek endocrinological attention...
October 12, 2016: Journal of Clinical Endocrinology and Metabolism
Marco Bonani, Ursina Meyer, Diana Frey, Nicole Graf, Heike A Bischoff-Ferrari, Rudolf P Wüthrich
BACKGROUND/AIMS: In a randomized controlled clinical trial in kidney transplant recipients (NCT01377467) we have recently shown that RANKL inhibition with denosumab significantly improved areal bone mineral density (aBMD) when given during the first year after transplantation. The effect of denosumab on skeletal microstructure and bone strength in kidney transplant recipients is not known. METHODS: The purpose of the present bone microarchitecture ancillary study was to investigate high-resolution peripheral quantitative computed tomography (HRpQCT) data from the distal tibia and distal radius in 24 study patients that had been randomized to receive either two injections of denosumab 60 mg at baseline and after 6 months (n=10) or no treatment (n=14)...
September 14, 2016: Kidney & Blood Pressure Research
Clifford J Rosen, Julie R Ingelfinger
No abstract text is available yet for this article.
September 18, 2016: New England Journal of Medicine
Felicia Cosman, Daria B Crittenden, Jonathan D Adachi, Neil Binkley, Edward Czerwinski, Serge Ferrari, Lorenz C Hofbauer, Edith Lau, E Michael Lewiecki, Akimitsu Miyauchi, Cristiano A F Zerbini, Cassandra E Milmont, Li Chen, Judy Maddox, Paul D Meisner, Cesar Libanati, Andreas Grauer
Background Romosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. Methods We enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck. Patients were randomly assigned to receive subcutaneous injections of romosozumab (at a dose of 210 mg) or placebo monthly for 12 months; thereafter, patients in each group received denosumab for 12 months, at a dose of 60 mg, administered subcutaneously every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months...
September 18, 2016: New England Journal of Medicine
Michael R McClung
No abstract text is available yet for this article.
September 15, 2016: Endocrine Practice
Ki-Chan An
Selective estrogen receptor modulators (SERMs) are now being used as a treatment for breast cancer, osteoporosis and postmenopausal symptoms, as these drugs have features that can act as an estrogen agonist and an antagonist, depending on the target tissue. After tamoxifen, raloxifene, lasofoxifene and bazedoxifene SERMs have been developed and used for treatment. The clinically decisive difference among these drugs (i.e., the key difference) is their endometrial safety. Compared to bisphosphonate drug formulations for osteoporosis, SERMs are to be used primarily in postmenopausal women of younger age and are particularly recommended if there is a family history of invasive breast cancer, as their use greatly reduces the incidence of this type of cancer in women...
August 2016: Asian Spine Journal
J Ward, C Wood, K Rouch, D Pienkowski, H H Malluche
UNLABELLED: Apparent modulus and failure stress of trabecular bone structure from 45 women with osteoporosis treated with bisphosphonates for varying durations were studied using finite element analyses and statistical modeling. Following adjustments for patient age and bone volume, increasing bisphosphonate treatment duration for up to 7.3 years was associated with treatment-time-dependent increases in bone apparent modulus and failure stress. Treatment durations exceeding 7.3 years were associated with time-dependent decreases in apparent modulus and failure stress from the peak values observed...
September 2016: Osteoporosis International
William D Leslie, Sumit R Majumdar, Suzanne N Morin, Lisa M Lix
Background: Whether change in bone mineral density (BMD) is an accurate indicator of antifracture effect in clinical practice is unknown. Objective: To evaluate repeated BMD testing as an indicator of treatment-related fracture risk reduction. Design: Registry-based cohort study. Setting: Manitoba, Canada. Patients: 6629 women aged 40 years or older initiating osteoporosis treatment with 2 consecutive dual-energy x-ray absorptiometry scans (mean interval, 4...
July 19, 2016: Annals of Internal Medicine
Takahiro Seno, Aihiro Yamamoto, Yuji Kukida, Aiko Hirano, Takashi Kida, Amane Nakabayashi, Kazuki Fujioka, Hidetake Nagahara, Wataru Fujii, Ken Murakami, Ryo Oda, Hiroyoshi Fujiwara, Masataka Kohno, Yutaka Kawahito
BACKGROUND: Patients with glucocorticoid-induced osteoporosis (GIOP) are at very high risk of fracture, and patients with severe GIOP often experience fractures during treatment with bisphosphonates. Teriparatide (TPTD) is the only currently available anabolic agent expected to be effective for GIOP. Once-weekly TPTD decreased bone resorption marker with primary osteoporosis different from daily TPTD, but it has not yet been tested with GIOP. OBJECTIVES: To evaluate the efficacy of once-weekly TPTD for patients with GIOP and inadequate response to bisphosphonates...
2016: SpringerPlus
Anne Camirand, David Goltzman, Ajay Gupta, Mohammadi Kaouass, Dibyendu Panda, Andrew Karaplis
Prolonged skeletal unloading through bedrest results in bone loss similar to that observed in elderly osteoporotic patients, but with an accelerated timeframe. This rapid effect on weight-bearing bones is also observed in astronauts who can lose up to 2% of their bone mass per month spent in Space. Despite the important implications for Spaceflight travelers and bedridden patients, the exact mechanisms involved in disuse osteoporosis have not been elucidated. Parathyroid hormone-related protein (PTHrP) regulates many physiological processes including skeletal development, and has been proposed as a mechanosensor...
2016: PloS One
R Coleman, T Powles, A Paterson, M Gnant, S Anderson, I Diel, J Gralow, G von Minckwitz, V Moebus, J Bergh, K I Pritchard, J Bliss, D Cameron, V Evans, H Pan, R Peto, R Bradley, R Gray
BACKGROUND: Bisphosphonates have profound effects on bone physiology, and could modify the process of metastasis. We undertook collaborative meta-analyses to clarify the risks and benefits of adjuvant bisphosphonate treatment in breast cancer. METHODS: We sought individual patient data from all unconfounded trials in early breast cancer that randomised between bisphosphonate and control. Primary outcomes were recurrence, distant recurrence, and breast cancer mortality...
October 3, 2015: Lancet
Jon J Vermeire, Brian M Suzuki, Conor R Caffrey
Hookworm infection is chief among soil-transmitted helminthiases (STHs) for the chronic morbidly inflicted. Deworming via mass drug administration (MDA) programs most often employs single doses of benzimidazole drugs to which resistance is a constant threat. To discover new drugs, we employ a hamster model of hookworm infection with Ancylostoma ceylanicum and use albendazole (ABZ; 10 mg/kg orally) as the gold standard therapy. We previously showed that a single oral 100 mg/kg dose of the cathepsin cysteine protease (CP) inhibitor, K11777, offers near cure of infection that is associated with a 95% reduction in the parasite's resident CP activity...
2016: Pharmaceuticals
Bo Abrahamsen, Pia Eiken, Daniel Prieto-Alhambra, Richard Eastell
OBJECTIVES:  To determine the skeletal safety and efficacy of long term (≥10 years) alendronate use in patients with osteoporosis. DESIGN:  Open register based cohort study containing two nested case control studies. SETTING:  Nationwide study of population of Denmark. PARTICIPANTS:  61 990 men and women aged 50-94 at the start of treatment, who had not previously taken alendronate, 1996-2007. INTERVENTIONS:  Treatment with alendronate...
2016: BMJ: British Medical Journal
Ken Garber
No abstract text is available yet for this article.
June 30, 2016: Nature Reviews. Drug Discovery
Emma Nolan, François Vaillant, Daniel Branstetter, Bhupinder Pal, Göknur Giner, Lachlan Whitehead, Sheau W Lok, Gregory B Mann, Kathy Rohrbach, Li-Ya Huang, Rosalia Soriano, Gordon K Smyth, William C Dougall, Jane E Visvader, Geoffrey J Lindeman
Individuals who have mutations in the breast-cancer-susceptibility gene BRCA1 (hereafter referred to as BRCA1-mutation carriers) frequently undergo prophylactic mastectomy to minimize their risk of breast cancer. The identification of an effective prevention therapy therefore remains a 'holy grail' for the field. Precancerous BRCA1(mut/+) tissue harbors an aberrant population of luminal progenitor cells, and deregulated progesterone signaling has been implicated in BRCA1-associated oncogenesis. Coupled with the findings that tumor necrosis factor superfamily member 11 (TNFSF11; also known as RANKL) is a key paracrine effector of progesterone signaling and that RANKL and its receptor TNFRSF11A (also known as RANK) contribute to mammary tumorigenesis, we investigated a role for this pathway in the pre-neoplastic phase of BRCA1-mutation carriers...
August 2016: Nature Medicine
Alison T Stopeck, Allan Lipton, Jean-Jacques Body, Guenther G Steger, Katia Tonkin, Richard H de Boer, Mikhail Lichinitser, Yasuhiro Fujiwara, Denise A Yardley, María Viniegra, Michelle Fan, Qi Jiang, Roger Dansey, Susie Jun, Ada Braun
PURPOSE: This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases. PATIENTS AND METHODS: Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n = 1,020) every 4 weeks...
December 10, 2010: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Zhou-Shan Tao, Bing-Li Bai, Xing-Wen He, Wei Liu, Hang Li, Qiang Zhou, Tao Sun, Zheng-Liang Huang, Kai-Kai Tu, Yang-Xun Lv, Wei Cui, Lei Yang
Surface modification techniques have been applied to generate titanium implant surfaces that promote osseointegration for the implants in cementless arthroplasty. However, its effect is not sufficient for osteoporotic bone. Strontium (Sr) promotes osteoblast proliferation and inhibits osteoclast proliferation and positively affects bone regeneration. The aim of this study was to confirm the effects of strontium-substituted hydroxyapatite (Sr-HA) coating via electrochemical deposition on implant's osseointegration in the osteoporotic condition...
April 21, 2016: Medical & Biological Engineering & Computing
Hamid Hassanzadeh, Varun Puvanesarajah, Alan C Dalkin
Over 50 million Americans have low bone mass. Poor bone quality is known to complicate spinal fusion surgery, which relies on strong bony purchase to be effective. Unfortunately, many spine surgeons do not perform routine workups for either osteoporosis or osteomalacia. Effective screening and risk factor assessment can allow for appropriate medical management of osteoporosis in the perioperative setting, improving outcomes. Medical management can be grouped into several different categories: vitamins and minerals, bisphosphonates, recombinant parathyroid hormone, estrogen replacement or modification, inhibitors of receptor activator of nuclear factor κ-B ligand (RANKL), and calcitonin...
May 2016: Clinical Spine Surgery
J N Tsai, A V Uihlein, S M Burnett-Bowie, R M Neer, N P Derrico, H Lee, M L Bouxsein, B Z Leder
CONTEXT: In postmenopausal osteoporosis, combining denosumab and teriparatide increases hip and spine bone mineral density more than either monotherapy. OBJECTIVE: The objective of the study was to determine the effects of 2 years of combination therapy on bone microarchitecture and estimated strength. DESIGN: This was an open-label, randomized controlled trial. PARTICIPANTS AND METHODS: We performed high-resolution peripheral quantitative computed tomography at the distal tibia and radius in 94 postmenopausal osteoporotic women randomized to 2 years of teriparatide 20 μg sc daily, denosumab 60 mg sc every 6 months, or both...
May 2016: Journal of Clinical Endocrinology and Metabolism
Gengyang Shen, Hui Ren, Ting Qiu, De Liang, Bo Xie, Zhida Zhang, Zhensong Yao, Zhidong Yang, Xiaobing Jiang
Imbalances between bone formation and resorption are the primary cause of osteoporosis. However, currently, a detailed molecular mechanism of osteoporosis is not available. Autophagy is the conserved process characterized by degrading and recycling aggregated proteins, intracellular pathogens, and damaged organelles. MicroRNAs (miRNAs) are novel regulatory factors that play important roles in numerous cellular processes, including autophagy, through the posttranscriptional regulation of gene expression. Conversely, autophagy plays a role in the regulation of miRNA homeostasis...
July 2016: Calcified Tissue International
2016-03-02 04:51:32
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