Joel S Finkelstein

Massachusetts General Hospital, Boston, Massachusetts, United States

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Publications (114)1412.22 Total impact

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    ABSTRACT: Epidemiologic data suggest that low serum 25-hydroxyvitamin D [25(OH)D] increases insulin resistance and the risk of type 2 diabetes. Few interventional trials have assessed the effect of vitamin D on insulin metabolism, and published results are discordant. The goal of this study was to perform a detailed assessment of the effect of ergocalciferol administration on glucose and insulin metabolism in healthy people with low total 25(OH)Dtotal. This was a 12-wk, double-blinded, randomized controlled trial. We enrolled 90 healthy volunteers aged 18-45 y with serum 25(OH)D ≤20 ng/mL (by immunoassay) and administered ergocalciferol 50,000 IU/wk or placebo for 12 wk. Primary endpoints were change in first-phase insulin response and insulin sensitivity as measured by intravenous glucose tolerance test. Secondary endpoints included change in homeostasis model assessment of insulin resistance; fasting glucose, insulin, and lipids; body mass index (BMI); and blood pressure. On-study 25(OH)Dtotal was assessed by liquid chromatography-tandem mass spectrometry. In the treated group, 25(OH)Dtotal rose from 18 ± 7 to 43 ± 12 ng/mL (P < 0.001) with no change in the placebo group. Despite this increase, at 12 wk, there were no between-group differences in either insulin response or insulin sensitivity, nor were there differences in any measured secondary endpoints. There was no evidence of effect modification by sex, race, glucose tolerance status, baseline 25(OH)Dtotal, or BMI. In healthy persons with low 25(OH)Dtotal, ergocalciferol administration for 12 wk normalizes 25(OH)Dtotal but does not improve insulin secretion, insulin sensitivity, or other markers of metabolic health. This trial was registered at as NCT00491322. © 2015 American Society for Nutrition.
    American Journal of Clinical Nutrition 07/2015; 102(2). DOI:10.3945/ajcn.115.111682 · 6.77 Impact Factor
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    ABSTRACT: Context: Low levels of serum 25 Hydroxyvitamin D (25(OH)D) have been linked to greater fracture risk in older women. Objective: To determine if higher 25(OH)D is associated with slower loss of bone mineral density (BMD) and lower fracture risk during the menopausal transition (MT). Design, Setting and Participants: Prospective cohort study at 5 US clinical centers. Mean age, 48.5 ± 2.7 years. The fracture analysis included 124 women with an incident traumatic fracture, 88 with incident non-traumatic fracture and 1532 women without incident fractures; average follow-up of 9.5 years. BMD analysis included 922 women with a documented final menstrual period. Main Outcome Measures: Serum 25(OH)D was measured by liquid chromatography tandem mass spectrometry at the third annual clinic visit. BMD was measured and incident fractures ascertained at each annual visit. Results: The mean 25(OH)D was 21.8 (ng/mL); 703 (43%) of the women had 25(OH)D values <20ng/mL. There was no significant association between 25(OH)D and traumatic fractures. In multivariable adjusted hazards models, the hazard ratio (HR) for non-traumatic fractures (95% confidence interval) was 0.72 (0.54, 0.95) for each 10 ng/mL increase in 25(OH)D. Comparing women whose 25(OH)D was ≥20 vs <20 ng/mL, the HR for fracture was 0.54 (0.32, 0.89). Changes in lumbar spine and femoral neck bone mineral density across menopause were not significantly associated with serum 25(OH)D level. Conclusion: Serum 25(OH)D levels are inversely associated with non-traumatic fracture in mid-life women. Vitamin D supplementation is warranted in midlife women with 25(OH)D levels below 20 ng/mL.
    Journal of Clinical Endocrinology &amp Metabolism 02/2015; 100(5):jc20144367. DOI:10.1210/jc.2014-4367 · 6.21 Impact Factor
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    ABSTRACT: Improvements in clinical care have led to increased life expectancy in patients with cystic fibrosis (CF) over the past several decades. Whether these improvements have had significant effects on bone health in patients with CF is unclear. This is a cross-sectional study comparing clinical characteristics and bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) in adults with CF evaluated in 1995-1999 to age-, race-, and gender-matched patients with CF evaluated in 2011-2013 at the same center on calibrated DXA machines. The cohorts were similar in terms of age, BMI, pancreatic insufficiency, presence of F508del mutation, and reproductive history. In the most recent cohort, pulmonary function was superior, and fewer patients had vitamin D deficiency or secondary hyperparathyroidism. Areal BMD measures of the PA spine, lateral spine, and distal radius were similarly low in the two cohorts. Although pulmonary function and vitamin D status were better in patients in the present-day cohort, areal BMD of the spine was reduced in a significant number of patients and was no different in patients with CF today than in the late 1990s. Further attention to optimizing bone health may be necessary to prevent CF-related bone disease. Copyright © 2015 European Cystic Fibrosis Society. All rights reserved.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 02/2015; 14(4). DOI:10.1016/j.jcf.2015.01.011 · 3.48 Impact Factor
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    ABSTRACT: Context: Bariatric surgery is increasingly popular but may lead to metabolic bone disease. Objective: To determine the rate of bone loss in the 24 months after Roux-en-Y gastric bypass. Design and Setting: Prospective cohort study conducted at an academic medical center. Participants: Adults with severe obesity, including 30 adults undergoing gastric bypass and 20 non-surgical controls. Outcomes: We measured bone mineral density (BMD) at the lumbar spine and proximal femur by quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) at 0, 12, and 24 months. BMD and bone microarchitecture were also assessed by high-resolution peripheral QCT (HR-pQCT), and estimated bone strength was calculated using micro-finite element analysis. Results: Weight loss plateaued 6 months after gastric bypass but remained greater than controls at 24 months (-37 ± 3 kg vs. -5 ± 3 kg p<0.001). At 24 months, BMD was 5-7% lower at the spine and 6-10% lower at the hip in subjects who underwent gastric bypass compared with non-surgical controls, as assessed by QCT and DXA (p<0.001 for all). Despite significant bone loss, average T-scores remained in the normal range 24 months after gastric bypass. Cortical and trabecular BMD and microarchitecture at the distal radius and tibia deteriorated in the gastric bypass group throughout the 24 months, such that estimated bone strength was 9% lower than controls. The decline in BMD persisted beyond the first year, with rates of bone loss exceeding controls throughout the second year at all skeletal sites. Mean serum calcium, 25(OH)-vitamin D, and PTH were maintained within the normal range in both groups. Conclusions: Substantial bone loss occurs throughout the 24 months after gastric bypass despite weight stability in the second year. Though the benefits of gastric bypass surgery are well established, the potential for adverse effects on skeletal integrity remains an important concern.
    Journal of Clinical Endocrinology &amp Metabolism 02/2015; 100(4):jc20144341. DOI:10.1210/jc.2014-4341 · 6.21 Impact Factor
  • Melissa S Putman · Mary L Bouxsein · Joel S Finkelstein ·

    Journal of Clinical Endocrinology &amp Metabolism 01/2015; 100(1):L9-L10. DOI:10.1210/jc.2014-4143 · 6.21 Impact Factor
  • E W Yu · M S Putman · N Derrico · G Abrishamanian-Garcia · J S Finkelstein · M L Bouxsein ·
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    ABSTRACT: Patients with type 2 diabetes mellitus (DM2) have increased fracture risk. We found that African-American women with DM2 have increased cortical porosity and lower cortical bone density at the radius than non-diabetic controls. These cortical deficits are associated with hyperglycemia and may contribute to skeletal fragility associated with DM2. Fracture risk is increased in patients with type 2 diabetes mellitus (DM2) despite normal areal bone mineral density (aBMD). DM2 is more common in African-Americans than in Caucasians. It is not known whether African-American women with DM2 have deficits in bone microstructure. We measured aBMD at the spine and hip by DXA, and volumetric BMD (vBMD) and microarchitecture at the distal radius and tibia by HR-pQCT in 22 DM2 and 78 non-diabetic African-American women participating in the Study of Women Across the Nation (SWAN). We also measured fasting glucose and HOMA-IR. Age, weight, and aBMD at all sites were similar in both groups. At the radius, cortical porosity was 26 % greater, while cortical vBMD and tissue mineral density were lower in women with DM2 than in controls. There were no differences in radius total vBMD or trabecular vBMD between groups. Despite inferior cortical bone properties at the radius, FEA-estimated failure load was similar between groups. Tibia vBMD and microarchitecture were also similar between groups. There were no significant associations between cortical parameters and duration of DM2 or HOMA-IR. However, among women with DM2, higher fasting glucose levels were associated with lower cortical vBMD (r = -0.54, p = 0.018). DM2 and higher fasting glucose are associated with unfavorable cortical bone microarchitecture at the distal radius in African-American women. These structural deficits may contribute to the increased fracture risk among women with DM2. Further, our results suggest that hyperglycemia may be involved in mechanisms of skeletal fragility associated with DM2.
    Osteoporosis International 11/2014; 26(2). DOI:10.1007/s00198-014-2927-7 · 4.17 Impact Factor
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    ABSTRACT: Proton pump inhibitors (PPIs) have been associated with diminished bone mineral density (BMD) and an increased risk of fracture, however prior studies have not yielded consistent results and many have sub-optimal ascertainment of both PPI use and BMD. We used data from the Study of Women's Health Across the Nation (SWAN), a multi-center, multi-ethnic community-based longitudinal cohort study of women across the menopause transition to examine the association between annualized BMD changes and new use of PPIs. We compared changes in BMD in new PPI users with changes in BMD in new users of Histamine 2 receptor antagonists (H2RAs) and with changes in BMD in subjects who did not use either class of medications. Mixed linear regression models included recognized risk factors for osteoporosis, including demographics, menopausal transition stage, BMI, lifestyle factors, as well as comorbidities and concomitant medications. To provide further evidence for the validity of our analytic approach, we also examined the effects of hormone therapy (HT), a class of medications that should reduce bone loss, on changes in BMD as an internal positive control group. We identified 207 new users of PPIs, 185 new users of H2RAs and 1,676 non-users. Study subjects had a mean age of 50 years and were followed for a median of 9.9 years. Adjusted models found no difference in the annualized BMD change at the lumbar spine, femoral neck or total hip in PPI users compared with H2RA users or non-users. These results were robust to sensitivity analyses. BMD increased as expected in HT users, supporting the validity of our study design. These longitudinal analyses plus similar prior studies argue against an association between PPI use and BMD loss. © 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 08/2014; 30(2). DOI:10.1002/jbmr.2344 · 6.83 Impact Factor
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    ABSTRACT: Context: Young adults with cystic fibrosis (CF) are at risk for low bone density and fractures, but the underlying alterations in bone microarchitecture that may contribute to their increased fracture risk are currently unknown. Objective: The main goal of this study was to utilize high resolution peripheral quantitative computed tomography (HR-pQCT) to characterize the bone micro-architecture, volumetric bone mineral density (vBMD), and estimated strength of the radius and tibia in young adults with CF compared to healthy volunteers. Design: Cross-sectional study. Setting: Outpatient clinical research center within a tertiary academic medical center. Participants: Thirty young adults with CF ages 18-40 years were evaluated and compared to 60 healthy volunteers matched by age (± 2 years), gender, and race. Intervention: N/A Main Outcome Measures: The primary outcomes were HR-pQCT-derived cortical and trabecular vBMD, bone microarchitecture, and estimates of bone strength. Results: At the radius and tibia, young adults with CF had smaller bone cross-sectional area and lower vBMD. Cortical and trabecular microarchitecture were compromised at both sites, most notably involving the trabecular bone of the tibia. These differences translated into lower estimated bone strength both at the radius and tibia. After accounting for BMI differences, young adults with CF had lower bone area and estimated bone strength at the radius and had compromised trabecular microarchitecture and lower total and trabecular vBMD and estimated bone strength at the tibia. Alterations in trabecular bone density and microarchitecture and estimated strength measures of the tibia were also greater than expected based on DXA-derived areal BMD differences. Conclusions: Young adults with CF have compromised bone microarchitecture and lower estimated bone strength at both the radius and tibia, even after accounting for their smaller body size. These skeletal deficits likely explain the higher fracture risk observed in young adults with CF.
    Journal of Clinical Endocrinology &amp Metabolism 06/2014; 99(9):jc20141982. DOI:10.1210/jc.2014-1982 · 6.21 Impact Factor
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    ABSTRACT: Context: The discovery of hypercalcemic diseases due to loss-of-function mutations in CYP24A1 has placed a new demand for sensitive and precise assays for 24,25-dihydroxyvitamin D. Objective: We describe a novel LC-MS/MS-based method involving derivatization with DMEQ-TAD to simultaneously assay multiple vitamin D metabolites including 25-OH-D and 24,25-(OH)2Dusing 100 μ l of serum with a 5-minute run-time. Design: The assay uses a newly-synthesized internal standard d6-24,25-(OH)2D3 enabling quantitation of 24,25-(OH)2D3, as well as the determination of the ratio of 25-OH-D3:24,25-(OH)2D3, a physiologically useful parameter. Setting: We report data on >1000 normal and disease samples involving D deficiency or hypercalcemia, as well as studies involving knockout mouse models. Results: The assay showed good correlation with samples from quality assurance schemes for 25-OH-D (25-OH-D2 and 25-OH-D3) determination (-2 to -5% bias), exhibited low inter- and intra-assay coefficients of variation (4-7%), and lower limits of quantitation of 0.25-0.45 nmol/L. In clinical studies, we found a strong correlation between serum levels of 25-OH-D3 and 24,25-(OH)2D3 (r(2)=0.80) in subjects over a broad range of 25-OH-D3 values and a marked lack of production of 24,25-(OH)2D3 below 25 nmol/L of 25-OH-D. The ratio of 25-OH-D3:24,25-(OH)2D3 which remained <25 in vitamin D sufficient subjects (serum 25-OH-D < 50 nmol/L) but was greatly elevated (80-100) in patients with idiopathic infantile hypercalcemia (IIH). Conclusions: The new method also showed good utility in clinical settings involving vitamin D deficiency, supplementation with vitamin D and IIH, as well as in animal models with ablation of selected CYPs involved in vitamin D.
    The Journal of Clinical Endocrinology and Metabolism 03/2014; 99(7):jc20134388. DOI:10.1210/jc.2013-4388 · 6.21 Impact Factor
  • Alexander V Uihlein · Joel S Finkelstein · Hang Lee · Benjamin Z Leder ·
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    ABSTRACT: Context: In-vitro and animal studies have reported conflicting results regarding an independent role for FSH in the regulation of bone turnover. Objective: To test the hypothesis that suppressing serum FSH while holding serum gonadal steroid levels stable in the eugonadal range will affect biochemical markers of bone metabolism in healthy men. Design: Randomized controlled trial. Setting: Tertiary care academic teaching hospital. Participants: Eugonadal men aged 20-50. Interventions: Participants received monthly GnRH analog injections to suppress FSH secretion plus daily topical testosterone gel in pre-specified doses (Intervention Group). Controls received matching placebos (Control Group). Subjects in the intervention group were individually matched with subjects in the control group to ensure that the mean testosterone and estradiol levels (measured every 4 weeks during the 16 week study period) in the 2 groups were similar. Main Outcome Measures: Biochemical markers of bone resorption (serum NTX and CTX), bone formation (serum osteocalcin), and FSH were measured at baseline and after 16 weeks of treatment. Results: Serum FSH declined by 2% in the control group and by 60% in the intervention group (P < 0.0001 for the between-group difference). Despite the substantial suppression of serum FSH in the intervention group, serum NTX, CTX, and osteocalcin did not change in the intervention group, nor were any between-group differences observed. Conclusion: When gonadal steroid levels are held constant, short-mid term suppression of FSH does not affect bone turnover in men. FSH does not appear to be a significant regulator of bone metabolism in eugonadal men.
    The Journal of Clinical Endocrinology and Metabolism 03/2014; 99(7):jc20133246. DOI:10.1210/jc.2013-3246 · 6.21 Impact Factor
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    ABSTRACT: Several studies, using dual-energy x-ray absorptiometry (DXA), have reported substantial bone loss after bariatric surgery. However, profound weight loss may cause artifactual changes in DXA areal bone mineral density (aBMD) results. Assessment of volumetric bone mineral density (vBMD) by quantitative computed tomography (QCT) may be less susceptible to such artifacts. We assessed changes in BMD of the lumbar spine and proximal femur prospectively for 1 year using DXA and QCT in 30 morbidly obese adults undergoing Roux-en-Y gastric bypass surgery and 20 obese non-surgical controls. At one year, subjects who underwent gastric bypass surgery lost 37 ± 2 kg compared with 3 ± 2 kg lost in the non-surgical controls (p < 0.0001). Spine BMD declined more in the surgical group than in the non-surgical group whether assessed by DXA (-3.3 vs. -1.1%, p = 0.034) or by QCT (-3.4 vs. 0.2%, p = 0.010). Total hip and femoral neck aBMD declined significantly in the surgical group when assessed by DXA (-8.9 vs. -1.1%, p < 0.0001 for the total hip and -6.1 vs. -2.0%, p = 0.002 for the femoral neck), but no changes in hip vBMD were noted using QCT. Within the surgical group, serum P1NP and CTX levels increased by 82 ± 10% and by 220 ± 22%, respectively, by 6 months and remained elevated over 12 months (p < 0.0001 for all). Serum calcium, vitamin D, and PTH levels remained stable in both groups. We conclude that moderate vertebral bone loss occurs in the first year after gastric bypass surgery. However, striking declines in DXA aBMD at the proximal femur were not confirmed with QCT vBMD measurements. These discordant results suggest that artifacts induced by large changes in body weight after bariatric surgery affect DXA and/or QCT measurements of bone, particularly at the hip.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2014; 29(3). DOI:10.1002/jbmr.2063 · 6.83 Impact Factor
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    ABSTRACT: Context: Anorexia nervosa (AN), a prevalent psychiatric disorder predominantly affecting women, is characterized by self-induced starvation and low body weight. Increased clinical fractures are common and most women have low bone mineral density (BMD). Previously investigated treatments have led to no or modest increases in BMD in AN. Objective: To investigate the effect of teriparatide [(hPTH-1-34), TPT], an anabolic agent, on low bone mass in women with AN. Design: Randomized, placebo-controlled Setting: Clinical Research Center Patients: 21 women with AN: 10 (mean age ± SEM: 47 ± 2.7 years) treated with TPT and 11 (47.1 ± 2.3 years) treated with placebo Interventions: TPT (20 mg SC) or placebo for six months Main outcome measures: Change in BMD of the spine and hip by dual-energy X-ray absorptiometry. Secondary outcome measures included changes in serum P1NP, CTX, sclerostin and IGF-I levels. Results: At six months, spine BMD increased significantly more with TPT [postero-anterior (PA) spine: 6.0 ± 1.4% and lateral spine: 10.5 ± 2.5%] compared to placebo (PA spine: 0.2 ± 0.7%; p<0.01 and lateral spine: -0.6 ± 1.0%; p<0.01). The results remained significant after controlling for baseline BMI, P1NP and IGF-I. Changes in femoral neck (p=0.4) and total hip (p=0.8) BMD were comparable in both groups, as were changes in weight. Serum P1NP levels increased after three months of TPT treatment and remained at this higher level at six months, whereas P1NP levels were unchanged in the placebo group (p=0.02). TPT was well tolerated by all subjects. Conclusions: This study demonstrates that TPT administration increases spine BMD substantially after only six months of therapy in women with AN.
    The Journal of Clinical Endocrinology and Metabolism 01/2014; 99(4):jc20134105. DOI:10.1210/jc.2013-4105 · 6.21 Impact Factor
  • Joel S Finkelstein · Elaine W Yu · Sherri-Ann M Burnett-Bowie ·
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    ABSTRACT: To the Editor: The meta-analysis by Shlipak et al. (Sept. 5 issue)(1) shows that a cystatin C-based estimated glomerular filtration rate (eGFR) offers improvements in predicting risks of death and end-stage renal disease across diverse populations. In their editorial, Ingelfinger and Marsden(2) caution that results cannot be applied to Asian and Hispanic patients except by extrapolation. Also, diabetes was underrepresented in the sample of patients with chronic kidney disease; it was present in only 9% of participants. Further, more information is still needed about the use of cystatin C in pregnant women, patients who have undergone renal transplantation, and children. ...
    New England Journal of Medicine 12/2013; 369(25):2457. DOI:10.1056/NEJMc1313169 · 55.87 Impact Factor
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    ABSTRACT: African-American women have a lower risk of fracture than Caucasian women, and this difference is only partially explained by differences in DXA areal bone mineral density (aBMD). Little is known about racial differences in skeletal microarchitecture and the consequences for bone strength. To evaluate potential factors underlying this racial difference in fracture rates, we used high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess cortical and trabecular bone microarchitecture and estimate bone strength using micro-finite element analysis in African-American (n = 100) and Caucasian (n = 173) women participating in the Study of Women's Health Across the Nation (SWAN). African-American women had larger and denser bones than Caucasians, with greater total area, aBMD, and total volumetric BMD (vBMD) at the radius and tibia metaphysis (p < 0.05 for all). African-Americans had greater trabecular vBMD at the radius, but higher cortical vBMD at the tibia. Cortical microarchitecture tended to show the most pronounced racial differences, with higher cortical area, thickness, and volumes in African-Americans at both skeletal sites (p < 0.05 for all), and lower cortical porosity in African-Americans at the tibia (p < 0.05). African-American women also had greater estimated bone stiffness and failure load at both the radius and tibia. Differences in skeletal microarchitecture and estimated stiffness and failure load persisted even after adjustment for DXA aBMD. The densitometric and microarchitectural predictors of failure load at the radius and tibia were the same in African-American and Caucasian women. In conclusion, differences in bone microarchitecture and density contribute to greater estimated bone strength in African-Americans and probably explain, at least in part, the lower fracture risk of African-American women.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 10/2013; 28(10). DOI:10.1002/jbmr.1953 · 6.83 Impact Factor
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    ABSTRACT: Current approaches to diagnosing testosterone deficiency do not consider the physiological consequences of various testosterone levels or whether deficiencies of testosterone, estradiol, or both account for clinical manifestations. We provided 198 healthy men 20 to 50 years of age with goserelin acetate (to suppress endogenous testosterone and estradiol) and randomly assigned them to receive a placebo gel or 1.25 g, 2.5 g, 5 g, or 10 g of testosterone gel daily for 16 weeks. Another 202 healthy men received goserelin acetate, placebo gel or testosterone gel, and anastrozole (to suppress the conversion of testosterone to estradiol). Changes in the percentage of body fat and in lean mass were the primary outcomes. Subcutaneous- and intraabdominal-fat areas, thigh-muscle area and strength, and sexual function were also assessed. The percentage of body fat increased in groups receiving placebo or 1.25 g or 2.5 g of testosterone daily without anastrozole (mean testosterone level, 44±13 ng per deciliter, 191±78 ng per deciliter, and 337±173 ng per deciliter, respectively). Lean mass and thigh-muscle area decreased in men receiving placebo and in those receiving 1.25 g of testosterone daily without anastrozole. Leg-press strength fell only with placebo administration. In general, sexual desire declined as the testosterone dose was reduced. The amount of testosterone required to maintain lean mass, fat mass, strength, and sexual function varied widely in men. Androgen deficiency accounted for decreases in lean mass, muscle size, and strength; estrogen deficiency primarily accounted for increases in body fat; and both contributed to the decline in sexual function. Our findings support changes in the approach to evaluation and management of hypogonadism in men. (Funded by the National Institutes of Health and others; number, NCT00114114.).
    New England Journal of Medicine 09/2013; 369(11):1011-22. DOI:10.1056/NEJMoa1206168 · 55.87 Impact Factor
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    ABSTRACT: Context:Concern has been raised that medications that block serotonin reuptake may affect bone metabolism, resulting in bone loss.Objective:The aim of the study was to compare annual bone mineral density (BMD) changes among new users of selective serotonin reuptake inhibitors (SSRIs), new users of tricyclic antidepressants (TCAs), and nonusers of antidepressant medications.Design and Setting:We conducted a prospective cohort study at five clinical centers in the United States.Participants:The study included 1972 community-dwelling women, aged 42 years and older, enrolled in the Study of Women's Health Across the Nation (SWAN).Exposure:The use of antidepressant medications was assessed by interview and verified from medication containers at annual visits. Subjects were categorized as nonusers (no SSRI or TCA use at any examination), SSRI users (initiated SSRI use after the baseline SWAN visit), or TCA users (initiated TCA use after the baseline visit), using a computerized dictionary to categorize type of medication.Main Outcome Measures:BMD at the lumbar spine, total hip, and femoral neck was measured using dual-energy x-ray absorptiometry at annual visits.Results:BMD was compared among 311 new users of SSRIs, 71 new users of TCAs, and 1590 nonusers. After adjustment for potential confounders, including age, race, body mass index, menopausal status, and hormone therapy use, mean lumbar spine BMD decreased on average 0.68% per year in nonusers, 0.63% per year in SSRI users (P = .37 for comparison to nonusers), and 0.40% per year in TCA users (P = .16 for comparison to nonusers). At the total hip and femoral neck, there was also no evidence that SSRI or TCA users had an increased rate of bone loss compared with nonusers. Results were similar in subgroups of women stratified by the Center for Epidemiologic Studies Depression Scale (<16 vs ≥16).Conclusions:In this cohort of middle-aged women, use of SSRIs and TCAs was not associated with an increased rate of bone loss at the spine, total hip, or femoral neck.
    The Journal of Clinical Endocrinology and Metabolism 09/2013; 98(11). DOI:10.1210/jc.2013-1971 · 6.21 Impact Factor
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    ABSTRACT: Objective: Our objective was to characterize changes in bone resorption in relation to the final menstrual period (FMP), reproductive hormones, body mass index (BMI), and ethnicity. Methods: Urinary type I collagen N-telopeptide (NTX), estradiol, and FSH levels were measured annually for up to 8 years spanning the menopause transition in 918 African American, Chinese, Japanese, or Caucasian women. Results: Urinary NTX began to increase sharply about 2 years before the FMP, reaching its peak level about 1 to 1.5 years after the FMP. NTX levels declined modestly from 2 to 6 years after the FMP but remained about 20% higher than before the menopause transition. The sharp rise in FSH occurred in conjunction with a sharp decline in estradiol and shortly after FSH levels began increasing rapidly. The mean increase in urinary NTX across the menopause transition was greatest in women with BMI <25 kg/m² and smallest in women with BMI >30 kg/m². Increases in NTX were greatest in Japanese women and smallest in African Americans. These differences were attenuated, but not eliminated, when analyses were adjusted for covariates, particularly BMI. Summary: During the menopause transition, a decline in ovarian function beginning about 2 years before the FMP is followed by an increase in bone resorption and subsequently by bone loss. The magnitude of the increase in bone resorption is inversely associated with BMI. Ethnic differences in changes in bone resorption are attenuated, but not eliminated, by adjustment for BMI. Ethnic differences in BMI, and corresponding ethnic differences in bone resorption, appear to account for much of the ethnic variation in perimenopausal bone loss.
    The Journal of Clinical Endocrinology and Metabolism 05/2013; 98(7). DOI:10.1210/jc.2012-4113 · 6.21 Impact Factor
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    ABSTRACT: Context:The associations of serum sex steroid and FSH levels with change of bone mineral density (BMD) across the complete menopausal transition are incompletely understood.Objective:The objective of the study was to examine the associations of annual serum levels of FSH, estradiol (E(2)), T, and SHBG with the rates of bone loss in 3 phases: pretransmenopausal [baseline to 1 year before the final menstrual period (FMP)], transmenopausal (1 year before to 2 years after the FMP), later postmenopausal (≥ 2 years after the FMP).Design:The design of the study was a repeated-measures, mixed-effects regression.Setting:This was a community-based observational study, with a 10-year follow-up.Participants:A total of 720 participants of the Study of Women's Health Across the Nation Bone Study participated in the study.Outcome Measures:Annualized lumbar spine (LS) and femoral neck (FN) BMD decline was measured.Results:The mean annual change in BMD was slowest in pretransmenopause (0.27%/year in FN) and fastest in transmenopause (2.16%/year in LS). In the pretransmenopausal phase, for every doubling of FSH level, LS BMD change was faster by -0.32%/year (P < .0001). In the transmenopausal phase, for every doubling of FSH level, LS BMD change was -0.35%/year faster (P < .0001); for every doubling of SHBG level, LS BMD change was -0.36%/year faster (P < .0001). In the later postmenopausal phase, for each doubling of the E(2) level, the LS BMD change was slower by +0.26%/year (P = .049); for each SHBG doubling, the LS BMD change was 0.21%/year slower (P = .048). The FN associations were weaker and inconsistent.Conclusions:Higher E(2) levels and lower FSH levels were associated with lower rates of LS bone loss in some but not all menopausal transition phases.
    The Journal of Clinical Endocrinology and Metabolism 02/2013; 98(4). DOI:10.1210/jc.2012-3651 · 6.21 Impact Factor
  • Elaine W Yu · Joel S Finkelstein ·

    JAMA The Journal of the American Medical Association 10/2012; 308(14):1428-1429. DOI:10.1001/jama.2012.12820 · 35.29 Impact Factor
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    ABSTRACT: Objective: Vitamin D deficiency is highly prevalent in high-risk patient populations, but the prevalence among otherwise healthy adults is less well-defined. The goal of this study was to determine the prevalence and predictors of low 25-hydroxyvitamin D (25OHD) levels in healthy younger adults.Methods: This was a cross-sectional study of 634 healthy volunteers aged 18-50 years performed between January, 2006 and May, 2008. We measured serum 25OHD and parathyroid hormone and recorded demographic variables including age, sex, race, and use of multivitamin (MVI) supplements.Results: 39% of subjects had 25OHD ≤ 20 ng/mL and 64% had 25OHD ≤ 30 ng/mL. Predictors of lower 25OHD levels included male sex, black or Asian race, and lack of MVI use (p < 0.001 foswr all predictors). Seasonal variation in 25OHD levels was present in the overall cohort but was not observed in MVI users. Lower 25OHD levels were associated with increased risk of elevated PTH. Regression models predicted 25OHD levels ≤ 20 or ≤ 30 ng/mL with areas under the receiver operating characteristic (ROC) curves of 0.76 and 0.80, respectively.Conclusion: Low 25OHD levels are prevalent in healthy adults and may confer risk of skeletal disease. Black and Asian adults are at increased risk of deficiency and MVI use appears partially protective. Our models predicting low 25OHD levels may guide decision-making regarding whom to screen for vitamin D deficiency.
    Endocrine Practice 09/2012; 18(6):1-26. DOI:10.4158/EP12072.OR · 2.81 Impact Factor

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  • 1987-2015
    • Massachusetts General Hospital
      • • Endocrine Unit
      • • Department of Medicine
      • • Neuroendocrine Unit
      • • Reproductive Endocrine Unit
      Boston, Massachusetts, United States
  • 1998-2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2004-2007
    • Brigham and Women's Hospital
      • • Division of Pharmacoepidemiology and Pharmacoeconomics
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 1996-2006
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2005
    • University of California, Davis
      Davis, California, United States
  • 2002-2004
    • University of Pittsburgh
      • Department of Psychiatry
      Pittsburgh, Pennsylvania, United States