Clifford J Rosen

Maine Medical Center Research Institute, Scarborough, Maine, United States

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Publications (332)2451.36 Total impact

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    ABSTRACT: Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation and low body weight. Women with AN have impaired bone formation, low bone mass and an increased risk of fracture. FGF-21 is a hormone secreted by the liver in starvation and FGF-21 transgenic mice have significant bone loss due to an uncoupling of bone resorption and bone formation. We hypothesized that FGF-21 may contribute to the low bone mass state of AN. We studied 46 women: 20 with AN (median age [interquartile range]: 27.5 [25, 30.75] years) and 26 normal-weight controls (NWC) of similar age (25 [24, 28.5] years). We investigated associations between serum FGF-21 and 1) aBMD measured by dual energy X-ray absorptiometry, 2) parameters of bone microarchitecture in the distal radius and tibia measured by high-resolution peripheral quantitative CT and 3) bone strength, estimated by microfinite element analysis. FGF-21 levels were similar in AN and NWC (AN: 33.1 [18.1, 117.0] pg/ml vs NWC: 57.4 [23.8, 107.1] pg/ml; p=0.54). There was a significant inverse association between log FGF-21 and trabecular number in the radius in both AN (R=-0.57, p<0.01) and NWC (R=-0.53, p<0.01) and a significant positive association between log FGF-21 and trabecular separation in the radius in AN (R=0.50, p<0.03) and NWC (R=0.52, p<0.01). Estimates of radial bone strength were inversely associated with log FGF-21 in AN (R=-0.50, p<0.03 for both stiffness and failure load). There were no associations between FGF-21 and aBMD, cortical parameters or tibial parameters in the AN or NWC groups. FGF-21 may be an important determinant of trabecular skeletal homeostasis in AN. Copyright © 2015. Published by Elsevier Inc.
    Bone 04/2015; DOI:10.1016/j.bone.2015.04.001 · 4.46 Impact Factor
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    ABSTRACT: Atypical antipsychotic (AA) drugs cause significant metabolic side effects and clinical data are emerging that demonstrate increased fracture risk and bone loss after treatment with the AA, risperidone (RIS). The pharmacology underlying the adverse effects on bone is unknown. However, RIS action in the central nervous system (CNS) could be responsible because the sympathetic nervous system (SNS) is known to uncouple bone remodeling. RIS treatment in mice significantly lowered trabecular bone volume fraction (BV/TV), due to increased osteoclast-mediated erosion and reduced osteoblast-mediated bone formation. Daytime energy expenditure was also increased and was temporally associated with the plasma concentration of RIS. Even a single dose of RIS transiently elevated expression of brown adipose tissue markers of SNS activity and thermogenesis, Pgc1a and Ucp1. Rankl, an osteoclast recruitment factor regulated by the SNS, was also increased 1 hr after a single dose of RIS. Thus, we inferred that bone loss from RIS was regulated, at least in part, by the SNS. To test this, we administered RIS or vehicle to mice that were also receiving the non-selective β-blocker propranolol (PRO). Strikingly, RIS did not cause any changes in trabecular BV/TV, erosion or formation while PRO was present. Furthermore, β2 adrenergic receptor null (Adrb2-/-) mice were also protected from RIS-induced bone loss. This is the first report to demonstrate SNS-mediated bone loss from any AA. Since AA medications are widely prescribed especially to young adults, clinical studies are needed to assess whether β-blockers will prevent bone loss in this vulnerable population.
    Endocrinology 04/2015; DOI:10.1210/en.2015-1099 · 4.64 Impact Factor
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    ABSTRACT: Multiple myeloma is a B-cell malignancy characterized by the unrelenting proliferation of plasma cells. Multiple myeloma causes osteolytic lesions and fractures that do not heal due to decreased osteoblastic and increased osteoclastic activity. However, the exact relationship between osteoblasts and myeloma cells remains elusive. Understanding the interactions between these dynamic bone-forming cells and myeloma cells is crucial to understanding how osteolytic lesions form and persist, and how tumors grow within the bone marrow. This review provides a comprehensive overview of basic and translational research focused on the role of osteoblasts in multiple myeloma progression and their relationship to osteolytic lesions. Importantly, current challenges for in vitro studies exploring direct osteoblastic effects on myeloma cells, and gaps in understanding the role of the osteoblast in myeloma progression are delineated. Finally, successes and challenges in myeloma treatment with osteoanabolic therapy (i.e. any treatment that induces increased osteoblastic number or activity) are enumerated. Our goal is to illuminate novel mechanisms by which osteoblasts may contribute to multiple myeloma disease progression and osteolysis to better direct research efforts. Ultimately, we hope this may provide a roadmap for new approaches to the pathogenesis and treatment of multiple myeloma with a particular focus on the osteoblast. Copyright © 2015. Published by Elsevier Inc.
    Bone 02/2015; 75. DOI:10.1016/j.bone.2015.02.021 · 4.46 Impact Factor
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    ABSTRACT: Obesity has been associated with high bone mineral density (BMD) but a greater propensity to fracture. Some obese individuals have increased marrow adipose tissue (MAT), but the impact of MAT on bone turnover remains controversial, as do changes in BMD associated with a high fat diet (HFD). In this study we hypothesized that MAT volume would increase in response to HFD but would be independent of changes in BMD. Hence, we fed C57BL/6J (B6) male mice at 3 weeks of age either a high fat diet (60 kcal %) or regular diet (10 kcal %) for 12 weeks (n = 10/group). We measured MAT volume by osmium staining and micro-CT (µCT) as well as bone parameters by µCT, histomorphometry, and dual-energy X-ray absorptiometry. We also performed a short-term pilot study using 13-week-old B6 males and females fed a HFD (58 kcal %) for 2 weeks (n = 3/sex). Both long- and short-term HFD feedings were associated with high MAT volume, however, femoral trabecular bone volume fraction (BV/TV), bone formation rate and cortical bone mass were not altered in the long-term study. In the short-term pilot study, areal BMD was unchanged after two weeks of HFD. We conclude that, for B6 mice fed a HFD starting at wean or 13 weeks of age, MAT increases whereas bone mass is not altered. More studies are needed to define the mechanism responsible for the rapid storage of energy in the marrow and its distinction from other adipose depots. This article is protected by copyright. All rights reserved
    Journal of Cellular Physiology 02/2015; DOI:10.1002/jcp.24954 · 3.87 Impact Factor
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    ABSTRACT: Obstructive sleep apnea (OSA) and low bone mass are two prevalent conditions, particularly among older adults, a section of the U.S. population that is expected to grow dramatically over the coming years. OSA, the most common form of sleep disordered breathing, has been linked to multiple cardiovascular, metabolic, hormonal and inflammatory derangements and may have adverse effects on bone. However, little is known about how OSA (including the associated hypoxia and sleep loss) affects bone metabolism. In order to gain insight into the relationship between sleep and bone, we review the growing information on OSA and metabolic bone disease and discuss the pathophysiological mechanisms by which OSA may affect bone metabolism/architecture. This article is protected by copyright. All rights reserved
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2015; 30(2). DOI:10.1002/jbmr.2446 · 6.59 Impact Factor
  • Anyonya R Guntur, Casey R Doucette, Clifford J Rosen
    01/2015; 4:621. DOI:10.1038/bonekey.2014.116
  • Mone Zaidi, Clifford Rosen, Alberta Zallone
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2015; 30(1). DOI:10.1002/jbmr.2402 · 6.59 Impact Factor
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    ABSTRACT: Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD. We validated DECT in pre-clinical and Phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in cadaver vertebrae and compared with DECT and WF-MRI. For a Phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12months after treatment. BMD and MF percent and distribution were quantified in lumbar vertebrae and the right femoral neck. Measured precision (3mg/cm(3)) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r=0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r=0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only by 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment. Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy. Copyright © 2014. Published by Elsevier Inc.
    Bone 12/2014; 73. DOI:10.1016/j.bone.2014.12.014 · 4.46 Impact Factor
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    ABSTRACT: Insulin like growth factor binding protein two (IGFBP-2) is important for acquisition of normal bone mass in mice; however, the mechanism by which IGFBP-2 functions is not defined. These studies investigated the role of IGFBP-2 in stimulating osteoblast differentiation. MC-3T3 preosteoblasts expressed IGFBP-2, and IGFBP-2 knockdown resulted in a substantial delay in osteoblast differentiation, reduced osteocalcin expression and Alizarin red staining. These findings were replicated in primary calvarial osteoblasts obtained from IGFBP-2 -/- mice and addition of IGFBP-2 rescued the differentiation program. In contrast, overexpression of IGFBP-2 accelerated the time course of differentiation as well as increasing the total number of differentiating cells. By day 6 IGFBP-2 overexpressing cells expressed twice as much osteocalcin as control cultures and this difference persisted. To determine the mechanism by which IGFBP-2 functions, the interaction between IGFBP-2 and receptor tyrosine phosphatase β (RPTPβ) was examined. Disruption of this interaction inhibited the ability of IGFBP-2 to stimulate AKT activation and osteoblast differentiation. Knockdown of RPTPβ enhanced osteoblast differentiation whereas overexpression of RPTPβ was inhibitory. Adding back IGFBP-2 to RPTPβ overexpressing cells was able to rescue cell differentiation via enhancement of AKT activation. To determine the region of IGFBP-2 that mediated this effect an IGFBP-2 mutant that contained substitutions of key amino acids in the heparin binding domain-1 (HBD-1) was prepared. This mutant had a major reduction in its ability to stimulate differentiation of calvarial osteoblasts from IGFBP-2 -/- mice. Addition of a synthetic peptide that contained the HBD-1 sequence to calvarial osteoblasts from IGFBP-2 -/- mice rescued differentiation and osteocalcin expression. In summary, the results clearly demonstrate that IGFBP-2 stimulates osteoblast differentiation and that this effect is mediated through its heparin binding domain-1 interacting with RPTPβ. The results suggest that stimulation of differentiation is an important mechanism by which IGFBP-2 regulates the acquisition of normal bone mass in mice. © 2014 American Society for Bone and Mineral Research.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 11/2014; 29(11). DOI:10.1002/jbmr.2282 · 6.59 Impact Factor
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    ABSTRACT: Observational studies suggest that vitamin D may lower the risk of type 2 diabetes. However, data from long-term trials are lacking. The Vitamin D and Type 2 Diabetes (D2d) study is a randomized clinical trial designed to examine whether a causal relationship exists between vitamin D supplementation and the development of diabetes in people at high risk for type 2 diabetes.
    Diabetes Care 09/2014; DOI:10.2337/dc14-1005 · 8.57 Impact Factor
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    ABSTRACT: Osteocyte activity is crucial to maintenance of bone quality. Sclerostin, an osteocyte product, inhibits bone formation, yet higher circulating sclerostin is associated with higher bone density (BMD). Bone marrow fat (MF) is associated with osteoporosis but little is known about the relationship between osteocyte activity and MF.
    08/2014; DOI:10.1210/jc.2013-4493
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    Nicolas Bonnet, Emmanuel Somm, Clifford J Rosen
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    ABSTRACT: Diets rich in omega-3s have been thought to prevent both obesity and osteoporosis. However, conflicting findings are reported, probably as a result of gene by nutritional interactions. Peroxisome proliferator-activated receptor-gamma (PPARγ), is a nuclear receptor that improves insulin sensitivity but causes weight gain and bone loss. Fish oil is a natural agonist for PPARγ and thus may exert its actions through PPARγ pathway. We examined the role of PPARγ in body composition changes induced by a fish or safflower oil diet using two strains of C57BL6J (B6); i.e. B6.C3H-6T (6T) congenic mice created by backcrossing a small locus on Chr 6 from C3H carrying 'gain of function' polymorphisms in the Pparγ gene onto a B6 background, and C57BL6J mice. After 9months of feeding both diets to female mice, body weight, percent fat and leptin levels were less in mice fed the fish oil vs those fed safflower oil, independent of genotype. At the skeletal level, fish oil preserved vertebral bone mineral density (BMD) and microstructure in B6 but not in 6T mice. Moreover, fish oil consumption was associated with an increase in bone marrow adiposity and a decrease in BMD, cortical thickness, ultimate force and plastic energy in femur of the 6T but not B6 mice. These effects paralleled an increase in adipogenic inflammatory and resorption markers in 6T but not B6. Thus, compared to safflower oil, fish oil (high ratio omega-3/-6) prevents weight gain, bone loss, and changes in trabecular microarchitecture in the spine with age. These beneficial effects are absent in mice with polymorphisms in the Pparγ gene (6T), supporting the tenet that the actions of n-3 fatty acids on bone microstructure are likely to be genotype dependent. Thus caution must be used in interpreting dietary intervention trials with skeletal endpoints in mice and in humans.
    Bone 07/2014; 68. DOI:10.1016/j.bone.2014.07.024 · 4.46 Impact Factor
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    ABSTRACT: PPARγ, a ligand-activated nuclear receptor, regulates fundamental aspects of bone homeostasis and skeletal remodeling. PPARγ-activating anti-diabetic thiazolidinediones in clinical use promote marrow adiposity, bone loss, and skeletal fractures. As such, delineating novel regulatory pathways that modulate the action of PPARγ, and its obligate heterodimeric partner RXR, may have important implications for our understanding and treatment of disorders of low bone mineral density. We present data here establishing retinaldehyde dehydrogenase 1 (Aldh1a1) and its substrate retinaldehyde (Rald) as novel determinants of PPARγ-RXR actions in the skeleton. When compared to wild type (WT) controls, retinaldehyde dehydrogenase-deficient (Aldh1a1(-/-)) mice were protected against bone loss and marrow adiposity induced by either the thiazolidinedione rosiglitazone or a high fat diet, both of which potently activate the PPARγ-RXR complex. Consistent with these results, Rald, which accumulates in vivo in Aldh1a1(-/-) mice, protects against rosiglitazone-mediated inhibition of osteoblastogenesis in vitro. In addition, Rald potently inhibits in vitro adipogenesis and osteoclastogenesis in WT mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) respectively. Primary Aldh1a1(-/-) HSCs also demonstrate impaired osteoclastogenesis in vitro compared to WT controls. Collectively, these findings identify Rald and retinoid metabolism through Aldh1a1 as important novel modulators of PPARγ-RXR transactivation in the marrow niche.
    Bone 07/2014; 67. DOI:10.1016/j.bone.2014.07.005 · 4.46 Impact Factor
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    ABSTRACT: The adipocyte-derived hormone adiponectin promotes metabolic and cardiovascular health. Circulating adiponectin increases in lean states such as caloric restriction (CR), but the reasons for this paradox remain unclear. Unlike white adipose tissue (WAT), bone marrow adipose tissue (MAT) increases during CR, and both MAT and serum adiponectin increase in many other clinical conditions. Thus, we investigated whether MAT contributes to circulating adiponectin. We find that adiponectin secretion is greater from MAT than WAT. Notably, specific inhibition of MAT formation in mice results in decreased circulating adiponectin during CR despite unaltered adiponectin expression in WAT. Inhibiting MAT formation also alters skeletal muscle adaptation to CR, suggesting that MAT exerts systemic effects. Finally, we reveal that both MAT and serum adiponectin increase during cancer therapy in humans. These observations identify MAT as an endocrine organ that contributes significantly to increased serum adiponectin during CR and perhaps in other adverse states.
    Cell Metabolism 07/2014; 20(2). DOI:10.1016/j.cmet.2014.06.003 · 16.75 Impact Factor
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    ABSTRACT: Women with anorexia nervosa (AN) have increased marrow fat despite severe depletion of body fat. Recent studies have suggested that marrow fat composition may serve as a biomarker for bone quality. The purpose of our study was to investigate marrow fat composition of the femur using proton MR spectroscopy (1H-MRS), and the relationship between measures of marrow fat composition and BMD and body composition in women with AN and normal-weight controls.
    Bone 06/2014; DOI:10.1016/j.bone.2014.06.014 · 4.46 Impact Factor
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    ABSTRACT: Lactation is associated with significant alterations in both body composition and bone mass. Systemic and local skeletal factors such as RANKL, PTHrP, calcitonin, and estrogen are known to regulate bone remodeling during and after lactation. FGF21 may function as an endocrine factor to regulate body composition changes during lactation by inducing gluconeogenesis and fatty acid oxidation. In this study, we hypothesized that the metabolic changes during lactation were due in part to increased circulating FGF-21, which in turn could accentuate bone loss. We longitudinally characterized body composition in C57BL/6J (B6) mice during (d7Lac and d21Lac) and after normal lactation (d21Post). At day 7(d7Lac) of lactation, areal bone density declined by 10% (aBMD: p<0.001) bone resorption increased (p<0.0001), percent fat decreased by 20%, energy expenditure increased (p<0.01), and markers of brown-like adipogenesis were suppressed in the inguinal depot and in pre-formed brown adipose tissue. At d7Lac there was a 2.4 fold increase in serum FGF-21 vs. baseline (p<0.0001), a 8-fold increase in hepatic FGF-21 mRNA (p<0.03), a 2-fold increase in undercarboxylated osteocalcin (p<0.01) and enhanced insulin sensitivity. Recovery of total aBMD was noted at d21Lac, while femoral trabecular bone volume fraction (BV/TV) was still reduced (p<0.01). Since FGF-21 levels rose rapidly at d7Lac in B6 lactating mice, we next examined lactating mice with a deletion in the Fgf21 gene. Trabecular as well as cortical bone mass were maintained throughout lactation in FGF-21-/- mice, while pup growth was normal. Compared to lactating control mice, lactating FGF-21-/- mice exhibited an increase in bone formation, but no change in bone resorption. In conclusion, in addition to changes in calcitropic hormones, systemic FGF-21 plays a role in skeletal remodeling and changes in body composition during lactation in B6 mice.
    Endocrinology 06/2014; 155(9):en20141083. DOI:10.1210/en.2014-1083 · 4.64 Impact Factor
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    ABSTRACT: Sef (similar expression to fgf genes) is a feedback inhibitor of fibroblast growth factor (FGF) signaling and functions in part by binding to FGF receptors and inhibiting their activation. Genetic studies in mice and humans indicate an important role for fibroblast growth factor signaling in bone growth and homeostasis. We therefore investigated whether Sef had a function role in skeletal acquisition and remodeling. Sef expression is increased during osteoblast differentiation in vitro, and LacZ staining of Sef + /- mice showed high expression of Sef in the periosteum and chondro-osseous junction of neonatal and adult mice. Mice with a global deletion of Sef showed increased cortical bone thickness, bone volume and increased periosteal perimeter by μCT. Histomorphometric analysis of cortical bone revealed a significant increase in osteoblast number. Interestingly, Sef-/- mice showed very little difference in trabecular bone by μCT and histomorphometry compared to wild type mice. Bone marrow cells from Sef-/- mice grown in osteogenic medium showed increased proliferation and increased osteoblast differentiation compared to wild type bone marrow cells. Bone marrow cells from Sef-/- mice showed enhanced FGF2-induced activation of the ERK pathway, whereas bone marrow cells from Sef transgenic mice showed decreased FGF2-induced signaling. FGF2-induced acetylation and stability of Runx2 was enhanced in Sef -/- bone marrow cells, whereas overexpression of Sef inhibited Runx2-responsive luciferase reporter activity. Bone marrow from Sef-/- mice showed enhanced hematopoietic lineage-dependent and osteoblast-dependent osteoclastogenesis and increased bone resorptive activity relative to wild type controls in in vitro assays, while overexpression of Sef inhibited osteoclast differentiation. Taken together, these studies indicate that Sef has specific roles in osteoblast and osteoclast lineages, and that its absence results in increased osteoblast and osteoclast activity with a net increase in cortical bone mass. © 2013 American Society for Bone and Mineral Research.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 05/2014; 29(5). DOI:10.1002/jbmr.2114 · 6.59 Impact Factor
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    ABSTRACT: Patient bone mineral density (BMD) predicts the likelihood of osteoporotic fracture. While substantial progress has been made toward elucidating the genetic determinants of BMD, our understanding of the factors involved remains incomplete. Here, using a systems genetics approach in the mouse, we predicted that bicaudal C homolog 1 (Bicc1), which encodes an RNA-binding protein, is responsible for a BMD quantitative trait locus (QTL) located on murine chromosome 10. Consistent with this prediction, mice heterozygous for a null allele of Bicc1 had low BMD. We used a coexpression network-based approach to determine how Bicc1 influences BMD. Based on this analysis, we inferred that Bicc1 was involved in osteoblast differentiation and that polycystic kidney disease 2 (Pkd2) was a downstream target of Bicc1. Knock down of Bicc1 and Pkd2 impaired osteoblastogenesis, and Bicc1 deficiency-dependent osteoblast defects were rescued by Pkd2 overexpression. Last, in 2 human BMD genome-wide association (GWAS) meta-analyses, we identified SNPs in BICC1 and PKD2 that were associated with BMD. These results, in both mice and humans, identify Bicc1 as a genetic determinant of osteoblastogenesis and BMD and suggest that it does so by regulating Pkd2 transcript levels.
    The Journal of clinical investigation 05/2014; 124(6). DOI:10.1172/JCI73072 · 13.77 Impact Factor
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    ABSTRACT: Purpose Abdominal adiposity is associated with low BMD and decreased growth hormone (GH) secretion, an important regulator of bone homeostasis. The purpose of our study was to determine the effects of a short course of GH on markers of bone turnover and bone marrow fat in premenopausal women with abdominal adiposity. Materials and Methods In a 6-month, randomized, double-blind, placebo-controlled trial we studied 79 abdominally obese premenopausal women (21-45y) who underwent daily sc injections of GH vs. placebo. Main outcome measures were body composition by DXA and CT, bone marrow fat by proton MR spectroscopy, P1NP, CTX, 25(OH)D, hsCRP, undercarboxylated osteocalcin (ucOC), preadipocyte factor 1 (Pref 1), apolipoprotein B (ApoB), and IGF-1. Results GH increased IGF-1, P1NP, 25(OH)D, ucOC, bone marrow fat and lean mass, and decreased abdominal fat, hsCRP, and ApoB compared with placebo (p < 0.05). There was a trend toward an increase in CTX and Pref-1. Among all participants, 6-month increase in IGF-1 correlated with 6-month increase in P1NP (p = 0.0005), suggesting that subjects with the greatest increases in IGF-1 experienced the greatest increases in bone formation. Six-month decrease in abdominal fat, hsCRP, and ApoB inversely predicted 6-month change in P1NP, and 6-month increase in lean mass and 25(OH)D positively predicted 6-month change in P1NP (p ≤ 0.05), suggesting that subjects with greatest decreases in abdominal fat, inflammation and ApoB, and the greatest increases in lean mass and 25(OH)D experienced the greatest increases in bone formation. Six-month increase in bone marrow fat correlated with 6-month increase in P1NP (trend), suggesting that subjects with the greatest increases in bone formation experienced the greatest increases in bone marrow fat. Forward stepwise regression analysis indicated that increase in lean mass and decrease in abdominal fat were positive predictors of P1NP. When IGF-1 was added to the model, it became the only predictor of P1NP. Conclusion GH replacement in abdominally obese premenopausal women for 6 months increased bone turnover and bone marrow fat. Reductions in abdominal fat, and inflammation, and increases in IGF-1, lean mass and vitamin D were associated with increased bone formation. The increase in bone marrow fat may reflect changes in energy demand from increased bone turnover.
    Bone 05/2014; DOI:10.1016/j.bone.2014.01.022 · 4.46 Impact Factor

Publication Stats

13k Citations
2,451.36 Total Impact Points

Institutions

  • 2008–2015
    • Maine Medical Center Research Institute
      Scarborough, Maine, United States
  • 2008–2014
    • Maine Medical Center
      Portland, Maine, United States
  • 2012
    • Tufts University
      Georgia, United States
    • University of North Carolina at Chapel Hill
      • Department of Medicine
      North Carolina, United States
    • Oregon State University
      • School of Biological and Population Health Sciences
      Corvallis, OR, United States
  • 2009–2011
    • Mount Sinai School of Medicine
      • • Division of Endocrinology, Diabetes and Bone Disease
      • • Department of Medicine
      Manhattan, NY, United States
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
    • Beverly Hospital, Boston MA
      BVY, Massachusetts, United States
  • 2000–2011
    • The Jackson Laboratory
      Bar Harbor, Maine, United States
    • Dalhousie University
      Halifax, Nova Scotia, Canada
  • 1999–2011
    • Creighton University
      Omaha, Nebraska, United States
    • Lady Davis Institute for Medical Research
      Montréal, Quebec, Canada
  • 1995–2010
    • St. Joseph's Hospital
      Savannah, Georgia, United States
  • 1994–2009
    • University of Maine
      Orono, Minnesota, United States
  • 2006
    • University of Texas Health Science Center at San Antonio
      • Department of Biochemistry
      San Antonio, Texas, United States
    • Brigham and Women's Hospital
      Boston, Massachusetts, United States
    • Cornell University
      • Department of Animal Science
      Итак, New York, United States
  • 2003–2005
    • University of California, San Francisco
      • Department of Epidemiology and Biostatistics
      San Francisco, CA, United States
    • National Institutes of Health
      베서스다, Maryland, United States
    • National Eye Institute
      Maryland, United States
  • 2002
    • Boston Children's Hospital
      Boston, Massachusetts, United States
    • Harvard University
      Cambridge, Massachusetts, United States
    • Columbia University
      • Department of Genetics and Development
      New York, New York, United States
  • 1996–1997
    • Husson College
      Saint Joseph, Missouri, United States
    • Society for Clinical Trials
      Society Hill, New Jersey, United States
  • 1992
    • Boston University
      Boston, Massachusetts, United States