Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Osteoporosis: HELP
Articles by Clifford J. Rosen
Based on 52 articles published since 2008

Between 2008 and 2019, C. Rosen wrote the following 52 articles about Osteoporosis.
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial Romosozumab - Promising or Practice Changing? 2017

Rosen, Clifford J. ·From Tufts University Medical School, Boston, and the Maine Medical Center Research Institute, Scarborough. ·N Engl J Med · Pubmed #28892459.

ABSTRACT: -- No abstract --

2 Editorial Building Better Bones with Biologics - A New Approach to Osteoporosis? 2016

Rosen, Clifford J / Ingelfinger, Julie R. ·From the Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough (C.J.R.). ·N Engl J Med · Pubmed #27641359.

ABSTRACT: -- No abstract --

3 Editorial Frailty: a D-ficiency syndrome of aging? 2010

Rosen, Clifford J / Manson, JoAnn E. · ·J Clin Endocrinol Metab · Pubmed #21131543.

ABSTRACT: -- No abstract --

4 Review Structure and Function of Bone Marrow Adipocytes. 2017

de Paula, Francisco José Albuquerque / Rosen, Clifford J. ·Department of Internal Medicine, Ribeirao Preto Medical School (FMRP), University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil. · Center for Clinical and Translational Research, Maine Medical Center Research Institute (MMCRI), Scarborough, Maine, USA. ·Compr Physiol · Pubmed #29357131.

ABSTRACT: Adipocytes are heterogeneous cells strongly linked to energy storage and disposal. In parallel, adipocytes are endowed with an extensive portfolio of endocrine molecules, whose secretion varies depending on nutritional status. Marrow adipose tissue (MAT) has specific characteristics that are not shared by white (WAT) or brown (BAT) adipose tissue. First, marrow adipocytes and osteoblasts are terminally differentiated cells that originate from the same bone marrow mesenchymal stromal cell. Differently from WAT adipocytes, marrow adipocytes expand under conditions of energy restriction and seem to be not influenced by energy surplus, at least in humans. Over the last few years, several lines of evidence have suggested that bone cells and MAT are mutually connected regarding the modulation of both energy metabolism and bone remodeling. Adipokines (e.g., adiponectin, leptin, and chemerin), incretins (GLP1 and GIP), and several classical hormones (e.g., GH and insulin) are biochemical components involved in the modulation of bone remodeling, marrow adipogenesis, and energy metabolism. As expected, metabolic and nutritional diseases such as diabetes mellitus and anorexia nervosa (AN) greatly affect MAT quantity and quality as well as bone strength. Although the interest in MAT started recently, the rapid advances in current technology have expedited unprecedented growth of knowledge in this area. The present review intends to give to the reader an up-to-date perspective about MAT structure and physiology as well as its involvement in metabolic and nutritional diseases such as diabetes mellitus and ano-rexia. © 2018 American Physiological Society. Compr Physiol 8:315-349, 2018.

5 Review Energy Metabolism of Bone. 2017

Motyl, Katherine J / Guntur, Anyonya R / Carvalho, Adriana Lelis / Rosen, Clifford J. ·1 Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, USA. · 2 Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine, USA. · 3 Internal Medicine Department, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil. ·Toxicol Pathol · Pubmed #29096593.

ABSTRACT: Biological processes utilize energy and therefore must be prioritized based on fuel availability. Bone is no exception to this, and the benefit of remodeling when necessary outweighs the energy costs. Bone remodeling is important for maintaining blood calcium homeostasis, repairing micro cracks and fractures, and modifying bone structure so that it is better suited to withstand loading demands. Osteoclasts, osteoblasts, and osteocytes are the primary cells responsible for bone remodeling, although bone marrow adipocytes and other cells may also play an indirect role. There is a renewed interest in bone cell energetics because of the potential for these processes to be targeted for osteoporosis therapies. In contrast, due to the intimate link between bone and energy homeostasis, pharmaceuticals that treat metabolic disease or have metabolic side effects often have deleterious bone consequences. In this brief review, we will introduce osteoporosis, discuss how bone cells utilize energy to function, evidence for bone regulating whole body energy homeostasis, and some of the unanswered questions and opportunities for further research in the field.

6 Review Energy Metabolism of the Osteoblast: Implications for Osteoporosis. 2017

Lee, Wen-Chih / Guntur, Anyonya R / Long, Fanxin / Rosen, Clifford J. ·Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri 63110. · Maine Medical Center Research Institute, Scarborough, Maine 04074. · Departments of Medicine and Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110. ·Endocr Rev · Pubmed #28472361.

ABSTRACT: Osteoblasts, the bone-forming cells of the remodeling unit, are essential for growth and maintenance of the skeleton. Clinical disorders of substrate availability (e.g., diabetes mellitus, anorexia nervosa, and aging) cause osteoblast dysfunction, ultimately leading to skeletal fragility and osteoporotic fractures. Conversely, anabolic treatments for osteoporosis enhance the work of the osteoblast by altering osteoblast metabolism. Emerging evidence supports glycolysis as the major metabolic pathway to meet ATP demand during osteoblast differentiation. Glut1 and Glut3 are the principal transporters of glucose in osteoblasts, although Glut4 has also been implicated. Wnt signaling induces osteoblast differentiation and activates glycolysis through mammalian target of rapamycin, whereas parathyroid hormone stimulates glycolysis through induction of insulin-like growth factor-I. Glutamine is an alternate fuel source for osteogenesis via the tricarboxylic acid cycle, and fatty acids can be metabolized to generate ATP via oxidative phosphorylation although temporal specificity has not been established. More studies with new model systems are needed to fully understand how the osteoblast utilizes fuel substrates in health and disease and how that impacts metabolic bone diseases.

7 Review Clinical Practice. Postmenopausal Osteoporosis. 2016

Black, Dennis M / Rosen, Clifford J. · ·N Engl J Med · Pubmed #26789873.

ABSTRACT: Key Clinical Points Postmenopausal Osteoporosis Fractures and osteoporosis are common, particularly among older women, and hip fractures can be devastating. Treatment is generally recommended in postmenopausal women who have a bone mineral density T score of -2.5 or less, a history of spine or hip fracture, or a Fracture Risk Assessment Tool (FRAX) score indicating increased fracture risk. Bisphosphonates (generic) and denosumab reduce the risk of hip, nonvertebral, and vertebral fractures; bisphosphonates are commonly used as first-line treatment in women who do not have contraindications. Teriparatide reduces the risk of nonvertebral and vertebral fractures. Osteonecrosis of the jaw and atypical femur fractures have been reported with treatment but are rare. The benefit-to-risk ratio for osteoporosis treatment is strongly positive for most women with osteoporosis. Because benefits are retained after discontinuation of alendronate or zoledronic acid, drug holidays after 5 years of alendronate therapy or 3 years of zoledronic acid therapy may be considered for patients at lower risk for fracture.

8 Review The bone-fat interface: basic and clinical implications of marrow adiposity. 2015

Devlin, Maureen J / Rosen, Clifford J. ·The University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: mjdevlin@umich.edu. · Maine Medical Center Research Institute, Scarborough, ME 04074, USA. ·Lancet Diabetes Endocrinol · Pubmed #24731667.

ABSTRACT: Obesity and osteoporosis are two of the most common chronic disorders of the 21st century. Both are accompanied by significant morbidity. The only place in the mammalian organism where bone and fat lie adjacent to each other is in the bone marrow. Marrow adipose tissue is a dynamic depot that probably exists as both constitutive and regulated compartments. Adipocytes secrete cytokines and adipokines that either stimulate or inhibit adjacent osteoblasts. The relationship of marrow adipose tissue to other fat depots is complex and might play very distinct parts in modulation of metabolic homoeostasis, haemopoiesis, and osteogenesis. Understanding of the relationship between bone and fat cells that arise from the same progenitor within the bone marrow niche provides insight into the pathophysiology of age-related osteoporosis, diabetes, and obesity.

9 Review Vitamin D and calcium: what do we need to know? 2013

Zhang, Vincent / Jiang, Xuezhi / Farukhi, Yousaf Z / Rosen, Clifford J / Schnatz, Peter F. ·Departments of *ObGyn; §Internal Medicine, The Reading Hospital and Medical Center, Reading; Departments of †ObGyn; ∥Internal Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania; ‡Maine Medical Center Research Institute, Portland, Maine. ·Clin Obstet Gynecol · Pubmed #24047935.

ABSTRACT: This chapter provides a summary of the literature including results from large trials, meta-analyses, and recent major recommendations. Two well-accepted and recent recommendations include those from the Agency for Health Research and Quality on calcium and vitamin D supplementation and from the Institute of Medicine's dietary reference intakes for calcium and vitamin D. This review suggests that there is strong evidence for synergistic roles of calcium and vitamin D in maintaining bone health in postmenopausal women, but the correlation between vitamin D alone and bone health is overall inconclusive.

10 Review In osteoporosis, differentiation of mesenchymal stem cells (MSCs) improves bone marrow adipogenesis. 2012

Pino, Ana María / Rosen, Clifford J / Rodríguez, J Pablo. ·Laboratorio de Biología Celular y Molecular, INTA, Universidad de Chile, Santiago, Chile. ·Biol Res · Pubmed #23283437.

ABSTRACT: The formation, maintenance, and repair of bone tissue involve close interlinks between two stem cell types housed in the bone marrow: the hematologic stem cell originating osteoclasts and mesenchymal stromal cells (MSCs) generating osteoblasts. In this review, we consider malfunctioning of MSCs as essential for osteoporosis. In osteoporosis, increased bone fragility and susceptibility to fractures result from increased osteoclastogenesis and insufficient osteoblastogenesis. MSCs are the common precursors for both osteoblasts and adipocytes, among other cell types. MSCs' commitment towards either the osteoblast or adipocyte lineages depends on suitable regulatory factors activating lineage-specific transcriptional regulators. In osteoporosis, the reciprocal balance between the two differentiation pathways is altered, facilitating adipose accretion in bone marrow at the expense of osteoblast formation; suggesting that under this condition MSCs activity and their microenvironment may be disturbed. We summarize research on the properties of MSCs isolated from the bone marrow of control and osteoporotic post-menopausal women. Our observations indicate that intrinsic properties of MSCs are disturbed in osteoporosis. Moreover, we found that the regulatory conditions in the bone marrow fluid of control and osteoporotic patients are significantly different. These conclusions should be relevant for the use of MSCs in therapeutic applications.

11 Review New insights into osteoporosis: the bone-fat connection. 2012

Kawai, M / de Paula, F J A / Rosen, C J. ·Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan. ·J Intern Med · Pubmed #22702419.

ABSTRACT: Osteoporosis and obesity are chronic disorders that are both increasing in prevalence. The pathophysiology of these conditions is multifactorial and includes genetic, environmental and hormonal determinants. Although it has long been considered that these are distinct disorders rarely found in the same individual, emerging evidence from basic and clinical studies support an important interaction between adipose tissue and the skeleton. It is proposed that adiposity may influence bone remodelling through three mechanisms: (i) secretion of cytokines that directly target bone, (ii) production of adipokines that influence the central nervous system thereby changing sympathetic impulses to bone and (iii) paracrine influences on adjacent skeletal cells. Here we focus on the current understanding of bone-fat interactions and the clinical implications of recent studies linking obesity to osteoporosis.

12 Review The 2011 IOM report on vitamin D and calcium requirements for north america: clinical implications for providers treating patients with low bone mineral density. 2011

Rosen, Clifford J / Gallagher, J Christopher. ·Maine Medical Research Institute, Scarborough, ME 04074, USA. crofen@gmail.com ·J Clin Densitom · Pubmed #21787514.

ABSTRACT: Vitamin D is an essential nutrient for skeletal mineralization and maintenance of bone mass. Most healthy individuals can meet their vitamin D requirements through dietary means, modest supplementation and solar exposure for short periods of time. The serum level of 25OHD that determines adequacy is 20 ng/ml, which corresponds with consumption of 6-800 IU of vitamin D per day, according to the Institute of Medicine review. There is still debate about whether higher doses of vitamin D are required for treating patients with osteoporosis.

13 Review Emerging therapeutic opportunities for skeletal restoration. 2011

Kawai, Masanobu / Mödder, Ulrike I / Khosla, Sundeep / Rosen, Clifford J. ·Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine, USA. ·Nat Rev Drug Discov · Pubmed #21283108.

ABSTRACT: Osteoporosis, a syndrome characterized by thin bones and fractures, has become more prevalent in both women and men. Established therapies for treating this disorder consist primarily of drugs that prevent bone loss, such as the bisphosphonates and selective oestrogen receptor modulators. Although these drugs have been shown to reduce fractures in randomized trials, there is an urgent need for treatments that could lower fracture risk further without additional adverse effects. The introduction of parathyroid hormone (teriparatide), which significantly increases bone mineral density, albeit for a relatively short duration, raised expectations that drugs that stimulate bone formation might cure osteoporosis. After outlining current approaches for treating osteoporosis, this Review focuses on emerging therapeutic opportunities for osteoporosis that are based on recent insights into skeletal physiology. Such novel strategies offer promise not only for reducing age-related bone loss and the associated risk of fractures but also for restoring bone mineral density to healthy levels.

14 Review Novel insights into the relationship between diabetes and osteoporosis. 2010

de Paula, Francisco J A / Horowitz, Mark C / Rosen, Clifford J. ·Center for Clinical and Translational Research, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA. ·Diabetes Metab Res Rev · Pubmed #20938995.

ABSTRACT: Only three decades ago adipose tissue was considered inert, with little relationship to insulin resistance. Similarly, bone has long been thought of purely in its structural context. In the last decade, emerging evidence has revealed important endocrine roles for both bone and adipose tissue. The interaction between these two tissues is remarkable. Bone marrow mesenchymal stem cells give rise to both osteoblasts and adipocytes. Leptin and adiponectin, two adipokines secreted by fat tissue, control energy homeostasis, but also have complex actions on the skeleton. In turn, the activities of bone cells are not limited to their bone remodelling activities but also to modulation of adipose cell sensitivity and insulin secretion. This review will discuss these new insights linking bone remodelling to the control of fat metabolism and the association between diabetes mellitus and osteoporosis.

15 Review PPARγ: a circadian transcription factor in adipogenesis and osteogenesis. 2010

Kawai, Masanobu / Rosen, Clifford J. ·Center for Clinical and Translational Research, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074-7205, USA. ·Nat Rev Endocrinol · Pubmed #20820194.

ABSTRACT: Peroxisome proliferator-activated receptor γ (PPARγ) is a critical factor for adipogenesis and glucose metabolism, but accumulating evidence demonstrates the involvement of PPARγ in skeletal metabolism as well. PPARγ agonists, the thiazolidinediones, have been widely used for the treatment of type 2 diabetes mellitus owing to their effectiveness in lowering blood glucose levels. However, the use of thiazolidinediones has been associated with bone loss and fractures. Thiazolidinedione-induced alterations in the bone marrow milieu-that is, increased bone marrow adiposity with suppression of osteogenesis-could partially explain the pathogenesis of drug-induced bone loss. Furthermore, several lines of evidence place PPARγ at the center of a regulatory loop between circadian networks and metabolic output. PPARγ exhibits a circadian expression pattern that is magnified by consumption of a high-fat diet. One gene with circadian regulation in peripheral tissues, nocturnin, has been shown to enhance PPARγ activity. Importantly, mice deficient in nocturnin are protected from diet-induced obesity, exhibit impaired circadian expression of PPARγ and have increased bone mass. This Review focuses on new findings regarding the role of PPARγ in adipose tissue and skeletal metabolism and summarizes the emerging role of PPARγ as an integral part of a complex circadian regulatory system that modulates food storage, energy consumption and skeletal metabolism.

16 Review Obesity, diabetes mellitus and last but not least, osteoporosis. 2010

Paula, Francisco J A de / Rosen, Clifford J. ·Departamento de Medicina Interna, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil. ·Arq Bras Endocrinol Metabol · Pubmed #20485903.

ABSTRACT: Knowledge about the influence of bone on intermediary metabolism corresponds to a developing area that has gained prominence. The old concept of bone and adipose tissues as inert metabolic tissues, with minor contributions to metabolic adaptations has been reconsidered in light of findings that bone is involved in the development of insulin sensitivity. Similarly adipose tissue exerts important influences on bone mass development and maintenance. Moreover, the use of drugs in the treatment of metabolic disorders such as diabetes mellitus can impact bone metabolism. These networks linking osteoporosis to obesity and diabetes mellitus have reinvigorated investigations in the pathophysiology of osteoporosis. The present review examines this aspect and calls attention to health care providers and potential treatments of skeletal disorder.

17 Review Bone loss or lost bone: rationale and recommendations for the diagnosis and treatment of early postmenopausal bone loss. 2009

Zaidi, Mone / Turner, Charles H / Canalis, Ernesto / Pacifici, Roberto / Sun, Li / Iqbal, Jameel / Guo, X Edward / Silverman, Stuart / Epstein, Solomon / Rosen, Clifford J. ·The Mount Sinai Bone Program, Box 1055, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA. mone.zaidi@mssm.edu ·Curr Osteoporos Rep · Pubmed #19968915.

ABSTRACT: Recent reports suggest that bone loss begins during late perimenopause at a dramatic rate, even before estrogen levels plummet. During the ensuing 5 years, there is evidence of the beginnings of microarchitectural deterioration, which impacts bone strength and ultimately enhances its propensity to fracture. The diagnosis of osteoporosis based on T-scores alone, or through stratification for a high fracture risk by FRAX, excludes these women who are rapidly losing bone. Because all antiosteoporosis therapies, in particular bisphosphonates, reduce bone loss, we propose aggressive, likely short-term therapy with a goal to reduce bone loss, stabilize bone density, and prevent microarchitectural deterioration.

18 Review Fat targets for skeletal health. 2009

Kawai, Masanobu / Devlin, Maureen J / Rosen, Clifford J. ·Maine Medical Center Research Institute, Scarborough, ME 04074-7205, USA. ·Nat Rev Rheumatol · Pubmed #19468288.

ABSTRACT: Emerging evidence points to a critical role for the skeleton in several homeostatic processes, including energy balance. The connection between fuel utilization and skeletal remodeling begins in the bone marrow with lineage allocation of mesenchymal stem cells to adipocytes or osteoblasts. Mature bone cells secrete factors that influence insulin sensitivity, and fat cells synthesize cytokines that regulate osteoblast differentiation; thus, these two pathways are closely linked. The emerging importance of the bone-fat interaction suggests that novel molecules could be used as targets to enhance bone formation and possibly prevent fractures. In this article, we discuss three pathways that could be pharmacologically targeted for the ultimate goal of enhancing bone mass and reducing osteoporotic fracture risk: the leptin, peroxisome proliferator-activated receptor gamma and osteocalcin pathways. Not surprisingly, because of the complex interactions across homeostatic networks, other pathways will probably be activated by this targeting, which could prove to be beneficial or detrimental for the organism. Hence, a more complete picture of energy utilization and skeletal remodeling will be required to bring any potential agents into the future clinical armamentarium.

19 Review Marrow fat and the bone microenvironment: developmental, functional, and pathological implications. 2009

Rosen, Clifford J / Ackert-Bicknell, Cheryl / Rodriguez, Juan Pablo / Pino, Ana Maria. ·Maine Medical Center Research Institute, Scarborough, ME 04041, USA. rofe@aol.com ·Crit Rev Eukaryot Gene Expr · Pubmed #19392647.

ABSTRACT: Bone marrow adipogenesis is a normal physiologic process in all mammals. However, its function is unknown. The mesenchymal stem cell is the marrow precursor for adipocytes as well as osteoblasts, and PPARG is an essential differentiation factor for entrance into the fat lineage. Mouse models have provided significant insight into the molecular cues that define stromal cell fate. In humans, accelerated marrow adipogenesis has been associated with aging and several chronic conditions, including diabetes mellitus and osteoporosis. Newer imaging techniques have been used to determine the developmental time course of fat generation in bone marrow. However, more studies are needed to understand the interrelationship among hematopoietic, osteoblastic, and adipogenic cells within the marrow niche.

20 Review Bone, fat, and body composition: evolving concepts in the pathogenesis of osteoporosis. 2009

Rosen, Clifford J / Klibanski, Anne. ·Maine Medical Center Research Institute, Scarborough, ME 04074, USA. rosenc@mmc.org ·Am J Med · Pubmed #19375545.

ABSTRACT: Disorders of body composition, including obesity and osteoporosis, have reached record proportions. Coincidentally, our understanding of the mechanisms controlling body mass also has greatly improved. Shared regulation at the hypothalamus and the bone marrow highlight major bone-fat interactions. The hypothalamus modulates fat and bone via the sympathetic nervous system by regulating appetite, insulin sensitivity, energy use, and skeletal remodeling. In the bone marrow, fat and bone cells arise from the same stem cells. Insights from disorders such as anorexia nervosa provide a new rationale for examining the mechanisms that link bone to fat. This article explores these relationships in the context of a new paradigm with implications for obesity and osteoporosis.

21 Clinical Trial Effects of PTH and alendronate on type I collagen isomerization in postmenopausal women with osteoporosis: the PaTH study. 2008

Garnero, Patrick / Bauer, Doug C / Mareau, Emmanuel / Bilezikian, John P / Greenspan, Susan L / Rosen, Clifford / Black, Dennis. ·INSERM Research Unit 664, Lyon, France ·J Bone Miner Res · Pubmed #18442311.

ABSTRACT: Fracture efficacy of PTH and alendronate (ALN) is only partly explained by changes in BMD, and bone collagen properties have been suggested to play a role. We analyzed the effects of PTH(1-84) and ALN on urinary alphaalpha/betabeta CTX ratio, a marker of type I collagen isomerization and maturation in postmenopausal women with osteoporosis. In the first year of the previously published PaTH study, postmenopausal women with osteoporosis were assigned to PTH(1-84) (100 microg/d; n = 119), ALN (10 mg/d; n = 60), or PTH and ALN together (n = 59). We analyzed patients on ALN alone (n = 60) and a similar number of patients assigned to PTH alone (n = 63). During the second year, women on PTH in the first year were reallocated to placebo (n = 31) or ALN (n = 32) and women with ALN continued on ALN. During the first year, there was no significant change in alphaalpha/betabeta CTX ratio with PTH or ALN. At 24 mo, there was a marked increase of the alphaalpha/betabeta CTX ratio in women who had received PTH during the first year, followed by a second year of placebo (median: +45.5, p < 0.001) or ALN (+55.2%, p < 0.001). Conversely, the alphaalpha/betabeta CTX ratio only slightly increased (+16%, p < 0.05) after 2 yr of continued ALN. In conclusion, treatment with PTH(1-84) for 1 yr followed by 1 yr of placebo or ALN may be associated with decreased type I collagen isomerization. The influence of these biochemical changes of type I collagen on bone fracture resistance remains to be studied.

22 Article FSH, Bone Mass, Body Fat, and Biological Aging. 2018

Zaidi, Mone / Lizneva, Daria / Kim, Se-Min / Sun, Li / Iqbal, Jameel / New, Maria I / Rosen, Clifford J / Yuen, Tony. ·The Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai, New York, New York. · Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. · Department of Reproductive Health Protection, Scientific Center of Family Health and Human Reproduction, Irkutsk, Russian Federation. · Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York. · Maine Medical Center Research Institute, Scarborough, Maine. ·Endocrinology · Pubmed #30085049.

ABSTRACT: The Study of Women's Health Across the Nation has taught us that impending ovarian failure during late perimenopause is associated with a sharp rise in serum FSH, which coincides with the most rapid rate of bone loss and the onset of visceral adiposity. At this time in a woman's life, serum estrogen levels are largely unaltered, so the hypothesis that hypoestrogenemia is the sole cause of bone loss and visceral obesity does not offer a full explanation. An alternative explanation, arising from animal models and human data, is that both physiologic aberrations, obesity and osteoporosis, arise at least in part from rising FSH levels. Here, we discuss recent findings on the mechanism through which FSH exerts biological actions on bone and fat and review clinical data that support a role for FSH in causing osteoporosis and obesity. We will also provide a conceptual framework for using a single anti-FSH agent to prevent and treat both osteoporosis and obesity in women across the menopausal transition.

23 Article Unsaturation level decreased in bone marrow fat of postmenopausal women with low bone density using high resolution magic angle spinning (HRMAS) 2017

Li, Xiaojuan / Shet, Keerthi / Xu, Kaipin / Rodríguez, Juan Pablo / Pino, Ana María / Kurhanewicz, John / Schwartz, Ann / Rosen, Clifford J. ·Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA. Electronic address: Xiaojuan.li@ucsf.edu. · Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA. · Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA. Electronic address: kaipin.xu@ucsf.edu. · Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile. Electronic address: jprodrig@inta.uchile.cl. · Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile. Electronic address: ampino@inta.uchile.cl. · Department of Radiology and Biomedical Imaging, University of California, San Francisco, USA. Electronic address: john.kurhanewicz@ucsf.edu. · Department of Epidemiology and Biostatistics, University of California, San Francisco, USA. Electronic address: ASchwartz@psg.ucsf.edu. · Maine Medical Center Research Institute, Scarborough, USA. ·Bone · Pubmed #28823880.

ABSTRACT: There are increasing evidences suggesting bone marrow adiposity tissue (MAT) plays a critical role in affecting both bone quantity and quality. However, very limited studies that have investigated the association between the composition of MAT and bone mineral density (BMD). The goal of this study was to quantify MAT unsaturation profile of marrow samples from post-menopausal women using ex vivo high-resolution magic angle spinning (HRMAS) proton nuclear magnetic resonance (

24 Article Blocking FSH induces thermogenic adipose tissue and reduces body fat. 2017

Liu, Peng / Ji, Yaoting / Yuen, Tony / Rendina-Ruedy, Elizabeth / DeMambro, Victoria E / Dhawan, Samarth / Abu-Amer, Wahid / Izadmehr, Sudeh / Zhou, Bin / Shin, Andrew C / Latif, Rauf / Thangeswaran, Priyanthan / Gupta, Animesh / Li, Jianhua / Shnayder, Valeria / Robinson, Samuel T / Yu, Yue Eric / Zhang, Xingjian / Yang, Feiran / Lu, Ping / Zhou, Yu / Zhu, Ling-Ling / Oberlin, Douglas J / Davies, Terry F / Reagan, Michaela R / Brown, Aaron / Kumar, T Rajendra / Epstein, Solomon / Iqbal, Jameel / Avadhani, Narayan G / New, Maria I / Molina, Henrik / van Klinken, Jan B / Guo, Edward X / Buettner, Christoph / Haider, Shozeb / Bian, Zhuan / Sun, Li / Rosen, Clifford J / Zaidi, Mone. ·Department of Medicine, and Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. · School and Hospital of Stomatology, Wuhan University, and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan, Hubei 430079, China. · Maine Medical Center Research Institute, Scarborough, Maine 04074, USA. · Department of Biomedical Engineering, Columbia University, New York, New York 10027, USA. · Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, Colorado 80045, USA. · Pathology Service, Greater Los Angeles Veterans Affairs Medical Center, Los Angeles, California 90073, USA. · Deparment of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania 19104, USA. · Proteomics Resource Center, Rockefeller University, New York, New York 10065, USA. · Department of Human Genetics and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2311 EZ Leiden, The Netherlands. · Department of Pharmaceutical and Biological Chemistry, University College London School of Pharmacy, London WC1N 1AX, UK. ·Nature · Pubmed #28538730.

ABSTRACT: Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the β-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the β-subunit of Fsh to block its action. Our studies uncover opportunities for simultaneously treating obesity and osteoporosis.

25 Article Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate. 2017

Fan, Yi / Hanai, Jun-Ichi / Le, Phuong T / Bi, Ruiye / Maridas, David / DeMambro, Victoria / Figueroa, Carolina A / Kir, Serkan / Zhou, Xuedong / Mannstadt, Michael / Baron, Roland / Bronson, Roderick T / Horowitz, Mark C / Wu, Joy Y / Bilezikian, John P / Dempster, David W / Rosen, Clifford J / Lanske, Beate. ·Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA 02115, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. · Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. · Maine Medical Center Research Institute, Scarborough, ME 04074, USA. · State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; Endocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA. · Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. · State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China. · Endocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA. · Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA 02115, USA; Endocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA. · Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02215, USA. · Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT 06510, USA. · Division of Endocrinology, Stanford University School of Medicine, Stanford, CA 94305, USA. · Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. · Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. · Maine Medical Center Research Institute, Scarborough, ME 04074, USA. Electronic address: rosenc@mmc.org. · Division of Bone and Mineral Research, Harvard School of Dental Medicine, Boston, MA 02115, USA; Endocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA. Electronic address: beate_lanske@hsdm.harvard.edu. ·Cell Metab · Pubmed #28162969.

ABSTRACT: Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots. By cell sorting, Pref1