Joel S. Finkelstein

Hypovitaminosis D in Medical Inpatients

BACKGROUND Vitamin D deficiency is a major risk factor for bone loss and fracture. Although hypovitaminosis D has been detected frequently in elderly and housebound people, the prevalence of vitamin D deficiency among patients hospitalized on a general medical service is unknown. METHODS We assessed vitamin D intake, ultraviolet-light exposure, and risk factors for hypovitaminosis D and measured serum 25-hydroxyvitamin D, parathyroid hormone, and ionized calcium in 290 consecutive patients on a general medical ward. RESULTS A total of 164 patients (57 percent) were considered vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, < or = 15 ng per milliliter), of whom 65 (22 percent) were considered severely vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, <8 ng per milliliter). Serum 25-hydroxyvitamin D concentrations were related inversely to parathyroid hormone concentrations. Lower vitamin D intake, less exposure to ultraviolet light, anticonvulsant-drug therapy, renal dialysis, nephrotic syndrome, hypertension, diabetes mellitus, winter season, higher serum concentrations of parathyroid hormone and alkaline phosphatase, and lower serum concentrations of ionized calcium and albumin were significant univariate predictors of hypovitaminosis D. Sixty-nine percent of the patients who consumed less than the recommended daily allowance of vitamin D and 43 percent of the patients with vitamin D intakes above the recommended daily allowance were vitamin D-deficient. Inadequate vitamin D intake, winter season, and housebound status were independent predictors of hypovitaminosis D in a multivariate model. In a subgroup of 77 patients less than 65 years of age without known risk factors for hypovitaminosis D, the prevalence of vitamin D deficiency was 42 percent. CONCLUSIONS Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily allowance and those without apparent risk factors for vitamin D deficiency.

Osteopenia in Men with a History of Delayed Puberty

BACKGROUND AND METHODS The effect of delayed puberty on peak bone mineral density in men is unknown. To determine whether such a delay reduces normal peak bone density and leads to osteopenia during adulthood, we measured radial bone mineral density by single-photon absorptiometry and spinal bone mineral density by dual-energy x-ray absorptiometry in 23 men who had a history of constitutionally delayed puberty and 21 men who underwent normal puberty. Their mean ages were 26 and 24 years, respectively. The groups were matched for other factors known to affect bone mass. RESULTS The mean (+/- SD) radial bone mineral density was significantly lower in the men with a history of delayed puberty than in the normal men (0.73 +/- 0.07 vs. 0.80 +/- 0.05 g per square centimeter; P less than 0.0002). Spinal bone mineral density was also significantly lower in the men with delayed puberty than in the normal men (1.03 +/- 0.10 vs. 1.13 +/- 0.11 g per square centimeter; P less than 0.003). Radial bone density was at least 1 SD below the mean value for the normal men in 15 of the 23 men with a history of delayed puberty, and spinal bone density was similarly decreased in 10 of the 23. CONCLUSIONS Adult men with a history of constitutionally delayed puberty have decreased radial and spinal bone mineral density. These findings suggest that the timing of puberty is an important determinant of peak bone density in men. Because the peak bone mineral density achieved during young adulthood is a major determinant of bone density in later life, men in whom puberty was delayed may be at increased risk for osteoporotic fractures when they are older.

Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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; ClinicalTrials.gov number, NCT00114114.).

Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women.

FGF‐23 is a novel regulator of phosphate metabolism. We studied the regulation of FGF‐23 by dietary phosphate in 66 men and women using two assays. Dietary phosphate restriction decreased FGF‐23 and loading increased FGF‐23 significantly. An assay that measured intact FGF‐23 showed the effects of dietary phosphate much more clearly than an assay that also measures presumed biologically inactive fragments. Dietary phosphate is a key regulator of circulating FGF‐23; choice of assay is critical when studying FGF‐23 physiology.

Randomized Controlled Trial of Annual Zoledronic Acid to Prevent Gonadotropin-Releasing Hormone Agonist–Induced Bone Loss in Men With Prostate Cancer

PURPOSE Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density (BMD) and increase fracture risk in men with prostate cancer. Annual zoledronic acid increases BMD in postmenopausal women, but its efficacy in hypogonadal men is not known. PATIENTS AND METHODS In a 12-month study, 40 men with nonmetastatic prostate cancer who were receiving a GnRH agonist and had T scores more than -2.5 were randomly assigned to zoledronic acid (4 mg intravenously on day 1 only) or placebo. BMD of the posteroanterior lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry. RESULTS Mean (+/- SE) BMD of the posteroanterior lumbar spine decreased by 3.1% +/- 1.0% in men assigned to placebo and increased by 4.0% +/- 1.0% in men assigned to zoledronic acid (P < .001). BMD of the total hip decreased by 1.9% +/- 0.7% in men assigned to placebo and increased by 0.7% +/- 0.5% in men assigned to zoledronic acid (P = .004). Similar between-group differences were observed for the femoral neck and trochanter. Serum N-telopeptide, a marker of osteoclast activity, decreased significantly after zoledronic acid treatment. CONCLUSION In men receiving a GnRH agonist, a single treatment with zoledronic acid significantly increased BMD and durably suppressed serum N-telopeptide levels for 12 months. Annual zoledronic acid may be a convenient and effective strategy to prevent bone loss in hypogonadal men.

Osteoporosis in Men: An Endocrine Society Clinical Practice Guideline

OBJECTIVE The aim was to formulate practice guidelines for management of osteoporosis in men. EVIDENCE We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and evidence quality. CONSENSUS PROCESS Consensus was guided by systematic evidence reviews, one in-person meeting, and multiple conference calls and e-mails. Task Force drafts were reviewed successively by The Endocrine Societys Clinical Guidelines Subcommittee and Clinical Affairs Core Committee; representatives of ASBMR, ECTS, ESE, ISCD; and members at large. At each stage, the Task Force received written comments and incorporated needed changes. The reviewed document was approved by The Endocrine Society Council before submission for peer review. CONCLUSIONS Osteoporosis in men causes significant morbidity and mortality. We recommend testing higher risk men [aged ≥70 and men aged 50-69 who have risk factors (e.g. low body weight, prior fracture as an adult, smoking, etc.)] using central dual-energy x-ray absorptiometry. Laboratory testing should be done to detect contributing causes. Adequate calcium and vitamin D and weight-bearing exercise should be encouraged; smoking and excessive alcohol should be avoided. Pharmacological treatment is recommended for men aged 50 or older who have had spine or hip fractures, those with T-scores of -2.5 or below, and men at high risk of fracture based on low bone mineral density and/or clinical risk factors. Treatment should be monitored with serial dual-energy x-ray absorptiometry testing.

Effects of Teriparatide, Alendronate, or Both in Women with Postmenopausal Osteoporosis

CONTEXT Teriparatide increases both bone formation and bone resorption. OBJECTIVE We sought to determine whether combining teriparatide with an antiresorptive agent would alter its anabolic action. DESIGN AND SETTING This was a randomized controlled trial conducted in a single university hospital. PATIENTS AND INTERVENTION We randomized 93 postmenopausal women with low bone mineral density (BMD) to alendronate 10 mg daily (group 1), teriparatide 40 microg sc daily (group 2), or both (group 3) for 30 months. Teriparatide was begun at month 6. MAIN OUTCOME MEASURES BMD of the lumbar spine, proximal femur, proximal radius, and total body was measured by dual-energy x-ray absorptiometry (DXA) every 6 months. Lumbar spine trabecular BMD was measured at baseline and month 30 by quantitative computed tomography. Serum osteocalcin, N-terminal propeptide of type 1 collagen, and N-telopeptide levels were assessed frequently. Women who had at least one repeat DXA scan on therapy were included in the analyses (n = 69). RESULTS DXA spine BMD increased more in women treated with teriparatide alone than with alendronate alone (18 +/- 11 vs. 7 +/- 4%; P < 0.001) or both (18+/-11 vs. 12 +/- 9%; P = 0.045). Similarly, femoral neck BMD increased more in women treated with teriparatide alone than with alendronate alone (11 +/- 5 vs. 4 +/- 4%; P < 0.001) or both (11 +/- 5 vs. 3 +/- 5%; P < 0.001). Quantitative computed tomography spine BMD increased 1 +/- 7, 61 +/- 31, and 24 +/- 24% in groups 1, 2, and 3 (P < 0.001 for all comparisons). Serum osteocalcin, N-terminal propeptide of type 1 collagen, and cross-linked N-telopeptides of type I collagen increased more with teriparatide alone than with both (P < 0.001 for each marker). CONCLUSION Alendronate reduces the ability of teriparatide to increase BMD and bone turnover in women.

Bicalutamide Monotherapy Versus Leuprolide Monotherapy for Prostate Cancer: Effects on Bone Mineral Density and Body Composition

PURPOSE Gonadotropin-releasing hormone agonists decrease bone mineral density, lean mass, and muscle size and increase fat mass in men with prostate cancer. Less is known about the effects of bicalutamide monotherapy on bone mineral density and body composition. PATIENTS AND METHODS In a 12-month, open-label study, we randomly assigned 52 men with prostate cancer and no bone metastases to receive either leuprolide or bicalutamide (150 mg by mouth daily). Bone mineral density and body composition were measured by dual energy x-ray absorptiometry and quantitative computed tomography. RESULTS Mean (+/- standard error) bone mineral density of the posterior-anterior lumbar spine decreased by 2.5% +/- 0.5% in the leuprolide group and increased by 2.5 +/- 0.5 in the bicalutamide group from baseline to 12 months (P <.001). Mean changes in bone mineral density of the total body, total hip, femoral neck, and trabecular bone of the lumbar spine also differed significantly between groups (P < or =.003 for each comparison). Fat mass increased by 11.1% +/- 1.3% in the leuprolide group and by 6.4% +/- 1.1% in the bicalutamide group (P =.01). Changes in lean mass, muscle size, and muscle strength were similar between the groups. Breast tenderness and enlargement were more common in the bicalutamide group than in the leuprolide group. Fatigue, loss of sexual interest, and vasomotor flushing were less common in the bicalutamide group than in the leuprolide group. CONCLUSION In men with prostate cancer, bicalutamide monotherapy increases bone mineral density, lessens fat accumulation, and has fewer bothersome side effects than treatment with a gonadotropin-releasing hormone agonist.

Low bone mineral density in hormone‐naïve men with prostate carcinoma

The objective of this study was to determine the prevalence of low bone mineral density in men with prostate carcinoma and no history of androgen‐deprivation therapy.

The association of endogenous hormone concentrations and bone mineral density measures in pre- and perimenopausal women of four ethnic groups: SWAN

Abstract We evaluated bone mineral density (BMD), hormone concentrations and menstrual cycle status to test the hypothesis that greater variations in reproductive hormones and menstrual bleeding patterns in mid-aged women might engender an environment permissive for less bone. We studied 2336 women, aged 42–52 years, from the Study of Womens Health Across the Nation (SWAN) who self-identified as African-American (28.2%), Caucasian (49.9%), Japanese (10.5%) or Chinese (11.4%). Outcome measures were lumbar spine, femoral neck and total hip BMD by dual-energy X-ray densitometry (DXA). Explanatory variables were estradiol, testosterone, sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) from serum collected in the early follicular phase of the menstrual cycle or menstrual status [premenopausal (menses in the 3 months prior to study entry without change in regularity) or early perimenopause (menstrual bleeding in the 3 months prior to study entry but some change in the regularity of cycles)]. Total testosterone and estradiol concentrations were indexed to SHBG for the Free Androgen Index (FAI) and the Free Estradiol Index (FEI). Serum logFSH concentrations were inversely correlated with BMD (r = −10 for lumbar spine [95% confidence interval (CI): −0.13, −0.06] and r = −0.08 for femoral neck (95% CI: −0.11, −0.05). Lumbar spine BMD values were approximately 0.5% lower for each successive FSH quartile. There were no significant associations of BMD with serum estradiol, total testosterone, FEI or FAI, respectively, after adjusting for covariates. BMD tended to be lower (p values = 0.009 to 0.06, depending upon the skeletal site) in women classified as perimenopausal versus premenopausal, after adjusting for covariates. Serum FSH but not serum estradiol, testosterone or SHBG were significantly associated with BMD in a multiethnic population of women classified as pre- versus perimenopausal, supporting the hypothesis that alterations in hormone environment are associated with BMD differences prior to the final menstrual period.