Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men

CONTEXT: The clinical value of measuring testosterone and estradiol in older men with osteoporosis and of measuring bone mineral density (BMD) in older men with testosterone or estradiol deficiency is uncertain. OBJECTIVE: The objective of the study was to examine the association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men. DESIGN: This study was a cross-sectional and longitudinal analysis. Setting: The study was conducted at six U.S. centers of the Osteoporotic Fractures in Men study. PARTICIPANTS: The study population consisted of 2447 community-dwelling men aged 65 yr or older. MAIN OUTCOME MEASURES: Total testosterone deficiency was defined as less than 200 ng/dl. Total estradiol deficiency was defined as less than 10 pg/ml. Osteoporosis was defined as femoral neck or total hip BMD T-score of -2.5 or less. Rapid bone loss was defined as 3%/yr or more. RESULTS: Prevalence of osteoporosis in men with deficient and normal total testosterone was 12.3 and 6.0% (P = 0.003) and 15.4 and 2.8% (P < 0.0001) in those with deficient and normal total estradiol. Among osteoporotic men and those with normal BMD, prevalence of total testosterone deficiency was 6.9 and 3.2% (P = 0.01), and prevalence of total estradiol deficiency was 9.2 and 2.4% (P = 0.0001). Incidence of rapid hip bone loss in men with deficient and normal total testosterone was 22.5 and 8.6% (p = 0.007) and in those with deficient and normal total estradiol was 14.3 and 6.3% (p = 0.08). CONCLUSIONS: Older men with total testosterone or estradiol deficiency were more likely to be osteoporotic. Those with osteoporosis were more likely to be total testosterone or estradiol deficient. Rapid hip bone loss was more likely in men with total testosterone deficiency. BMD testing of older men with sex steroid deficiency may be clinically warranted.     

Infertility in men with inflammatory bowel disease

Inflammatory bowel disease(IBD) predominantly affects young adults. Fertility-related issues are therefore im-portant in the m-anagem-ent of patients with IBD. However, relatively m-odest attention has been paid to reproductive issues faced by m-en with IBD. To investigate the effects of IBD and its treatm-ent on m-ale fertility, we reviewed the current literature using a system-atic search for published studies. A PubM ed search were perform-ed using the m-ain search term-s "IBD AND m-ale infertility", "Crohn's disease AND m-ale infertility", "ulcerative colitis AND m-ale infertility". References in review articles were used if relevant. We noted that active inflammation, poor nutrition, alcohol use, sm-oking, m-edications, and surgery m-ay cause infertility in m-en with IBD. In surgery such as proctocolectom-y with ileal pouch-anal anastom-osis, rectal incision seem-s to be associated with sexual dysfunction. Of the m-edications used for IBD, sulfasalazine reversibly reduces m-ale fertility. No other m-edications appear to affect m-ale fertility significantly, although sm-all studies suggested som-e adverse effects. There are lim-ited data on the effects of drugs for IBD on m-ale fertility and pregnancy outcom-es; however, patients should be inform-ed of the possible effects of paternal drug exposure. This review provides inform-ation on fertility-related issues in m-en with IBD and discusses treatm-ent options.     

Association of hyperhomocysteinemia and folate deficiency with colon tumors in patients with inflammatory bowel disease

BACKGROUND: Folate deficiency associated with hyperhomocysteinemia might increase the risk of developing colorectal cancer. The aim of this study was to evaluate factors associated with colonic carcinogenesis, in particular, folate and homocysteinemia levels, in a cross-sectional study of patients with inflammatory bowel disease (IBD). METHODS: IBD patients with carcinogenic lesions discovered during colonoscopy [dysplasia-associated lesion or masses (DALM), colorectal cancer] were included and compared with the whole population of IBD patients with a normal colonoscopy performed during the same period. The following parameters were collected at the time of colonoscopy: age, sex, type, duration, activity, and extent of the disease, treatment, smoking status, and vitamin B12, folate, and homocysteinemia levels. Univariate and multivariate analyses were performed after adjusting for the main parameters. RESULTS: One hundred and fourteen patients [41 with ulcerative colitis (UC), 73 with Crohn's disease (CD)] were included. Twenty-six carcinogenic lesions were isolated: 18 DALM (7 high-grade and 11 low-grade dysplasia) and 8 colorectal cancers. In univariate analysis, the factors associated with carcinogenesis were: active smoking (P = 0.03), folate level < 145 pmol/L (P = 0.02), hyperhomocysteinemia > 15 micromol/L (P = 0.003), duration of disease > 10 years (P = 0.006), and UC (P = 0.02). In multivariate analysis, patients with hyperhomocysteinemia associated with folate deficiency had 17 times as many carcinogenic lesions as patients with normal homocysteinemia whatever the folate status and duration of the disease (P = 0.01). Patients with hyperhomocysteinemia without folate deficiency had 2.5 times as many carcinogenic lesions as patients with normal homocysteinemia (P = 0.08). CONCLUSIONS: Our data suggest that in IBD patients with normal homocysteinemia, the increase in carcinogenic risk is negligible. Conversely, in patients with hyperhomocysteinemia, folate deficiency may be associated with increased colorectal carcinogenesis in IBD patients.     

Iron deficiency in inflammatory bowel disease

The prevalence of iron-deficiency anemia was defined in 105 patients with inflammatory bowel disease and an appraisal made of the diagnostic value of serum ferritin for the assessment of iron stores. Iron deficiency, defined by the absence of bone-marrow hemosiderin was found with anemia in 36% of 41 patients with ulcerative colitis (UC) and 22% of 64 patients with Crohn's disease (CD). Iron deficiency without impaired erythropoiesis was detected in an additional 32% of patients with UC and 2% with CD. Anemia with plentiful bone-marrow iron was present in 33 (51%) of patients with CD, only one of whom had vitamin B₁₂ deficiency. Red blood cell morphology, RBC indices, serum iron, and percent transferrin saturation correlated poorly with stainable marrow iron. Serum ferritin, assayed in samples from 45 patients, was <18 ng/ml in 4/12 with iron-deficiency anemia and 0/5 with absent marrow iron and a normal hemoglobin level; values >55 ng/ml were invariably associated with the presence of marrow hemosiderin. Based on a lower normal limit of 18 ng/ml, the serum ferritin had an excellent predictive value (100%) but a high predictive error (32%) in the diagnosis of iron deficiency in inflammatory bowel disease. Serum ferritin >55 ng/ml ruled out iron deficiency as the basis for anemia.     

Infliximab and semen quality in men with inflammatory bowel disease

BACKGROUND: Infliximab is effective for induction and maintenance of remission in reproductive age men with Crohn's disease. There is no available data on the effects of infliximab on semen quality. The aim of this study was to determine whether changes in semen quality occurred in men receiving infliximab. METHODS: In this prospective study, each patient served as his own control. Patients completed general health and fertility questionnaires and were assessed for disease activity. Two semen analyses were completed before infusion with infliximab and 1 semen analysis was completed 1 week after infusion. Mean semen parameters before infusion were compared with postinfusion parameters by paired t tests. RESULTS: Ten men completed the study. Seven were on maintenance infliximab (group 1) and 3 were receiving a first dose (group 2). Seven had Crohn's disease, 2 had indeterminate colitis, and 1 had ulcerative colitis. All group 1 patients were in remission. Group 2 patients had moderate or severe disease. In comparing pre- and postinfusion semen parameters in all 10 patients, there was a significant increase in semen volume (P = 0.013) after infusion with infliximab and a trend toward decreased sperm motility (P = 0.061). Group 1 had a significant increase in semen volume after infusion (P = 0.039) and a significant decrease in normal oval forms after infusion (P = 0.038). In comparing group 1 and group 2, there was a significant difference in sperm progression. CONCLUSIONS: Infliximab therapy in men may decrease sperm motility and the number of normal oval forms. Whether these findings translate into impaired fertility is an area for further study.     

Metabolic bone disease in inflammatory bowel disease

Osteoporosis is associated with a high morbidity rate and is a risk factor for fractures. Patients with inflammatory bowel disease are at increased risk of developing osteopenia and osteoporosis. Corticosteroid use, malnutrition, and proinflammatory cytokines are unique risk factors for bone loss in ulcerative colitis and Crohn disease. Bone mineral density is assessed by dual-energy X-ray absorptiometry and reported as a T score or number of standard deviations away from the mean. A T score < 1 SD below the mean is normal, 1 to 2.5 SD below the mean is consistent with osteopenia, and greater than 2.5 SD below the mean is defined as osteoporosis. Treatment includes a combination of basic preventative measures, for example, weight-bearing exercise, calcium, vitamin D, and pharmacologic agents, (e.g., bisphosphonates).     

Anaemia and iron deficiency in children with inflammatory bowel disease

Background and aimsAnaemia and iron deficiency are common in children with Inflammatory Bowel Disease (IBD) however it is not known if the prevalence of anaemia and iron deficiency alters following diagnosis.MethodsLaboratory results from diagnosis, and at follow up one and two years later were recorded retrospectively in children with IBD recruited from a tertiary centre. Anaemia was defined using WHO standards and iron deficiency defined using published guidelines.Results46 children (16 girls) with Crohn's disease and 34 children (18 girls) with UC were studied. 75% of children with IBD were anaemic at diagnosis, 30% were anaemic at follow up two years later. 90% of children with Crohn's and 95% of children with Ulcerative Colitis (UC) were iron deficient at diagnosis. At follow up two years later 70% of children with Crohn's and 65% of children with UC were iron deficient.ConclusionsPersistent anaemia and iron deficiency are common in childhood IBD, prevalence alters with duration of time from diagnosis.     

Iron deficiency anemia in inflammatory bowel disease

Anemia is a common extraintestinal manifestation of inflammatory bowel disease(IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia(IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used labora-tory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and con-venient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD.     

Metabolic bone disease in adults with inflammatory bowel disease.

Bone loss is seen frequently in those with inflammatory bowel disease (IBD). It appears to be more common in those with Crohn's disease than in those with ulcerative colitis. Corticosteroids play an important role in the development of osteoporosis. The prevalence of osteoporosis in IBD, the effects of corticosteroids on bone metabolism, and treatment options are reviewed.     

Relation of age and smoking to serum levels of total testosterone and dehydroepiandrosterone sulfate in aged men

Background:   Hormonal factors have been extensively investigated in the area of geriatric medicine in the search for potential anti-aging agents or useful biomarkers for senescence in men. However, inconsistent results have been published so far concerning the relation of anthropometric and life-style factors to endocrine factors. To confirm the relationships between epidemiological parameters and sex hormone levels, we examined the relation of age and smoking to serum levels of total testosterone (T) and dehydroepiandrosterone sulfate (DHEA) in aged men.
Methods:   The subjects included men aged 50–74 years, 40 current smokers and 27 never smokers. Serum levels of T and DHEA were assayed with a radioimmunoassay kit.
Results:   Serum T did not decrease with age, and was significantly higher in smokers than for non-smokers. Serum DHEA decreased with age more sharply in non-smokers than for smokers.
Conclusion:   These data suggest that serum DHEA decreases with aging, but serum T does not, and that serum levels of these hormones are influenced by cigarette smoking.     

炎症性肠病与骨质疏松研究进展

骨质疏松是炎症性肠病(IBD)患者常见但易被忽视的并发症之一.炎症性肠病患者骨质疏松的发病机制尚未完全明了,皮质类固醇激素的应用、炎性细胞因子的增加、维生素D的缺乏及遗传等众多因素均可能参与骨质疏松的发生.对于炎症性肠病患者并发骨质疏松者应及早诊断及治疗,早期干预可减轻IBD患者骨质疏松的发生与发展.     

Plasma dehydroepiandrosterone sulfate in nursing home men

Previous studies have shown the normal range of plasma dehydroepiandrosterone sulfate (DHEAS) for independent community men over 60 years old to be 30-200 micrograms/dL. In human adults, low levels of plasma DHEAS have been correlated with a high mortality rate. In rodents, dehydroepiandrosterone, the precursor of DHEAS, has exhibited antidiabetic, anticarcinogenic, neurotropic, and memory-enhancing effects. We have now measured plasma DHEAS in 50 independent community men age 55-94 and in 61 nursing home men age 57-104. Mean DHEAS was significantly lower in the nursing home men than in the community men. Plasma DHEAS was subnormal (less than 30 micrograms/dL) in 40% of the nursing home residents and in only 6% of the community subjects. In both groups, DHEAS was inversely related to age. In the nursing home men, additionally, plasma DHEAS was inversely related to the presence of an organic brain syndrome and to the degree of dependence in activities of daily living. Plasma DHEAS was subnormal in 80% of the nursing home men who required total care. There was no significant correlation between the plasma concentrations of DHEAS and testosterone, or between plasma DHEAS and one-year mortality rate.     

Association of coeliac disease and inflammatory bowel disease.

The association of coeliac disease and inflammatory bowel disease is rare, as only three individual cases have been reported. Four additional cases of the association are described. A review of the prevalence figures for the two disorders suggests that this is more than a chance association.     

炎症性肠病与骨代谢研究若干进展

骨质疏松(OP)是炎症性肠病(IBD)患者常见但易被忽视的并发症之一.IBD患者骨代谢异常的发病机制除了营养不良,钙、磷吸收异常,性腺功能减退之外,还与使用激素,炎症因子的异常活化等紧密相关.研究发现IBD患者骨质疏松发生率在15%左右,在老年IBD患者身上表现尤为显著,使用激素是其主要危险因子.IBD患者骨折发生率并没有原先预期的那么高.骨代谢指标对预测IBD患者BMD及骨折发生价值有限.     

炎症性肠病患者骨代谢状况评估

目的 了解炎症性肠病(IBD)患者骨代谢生化指标的变化特点,评估其与骨质疏松和(或)骨量减少间的关系,探寻IBD患者发生骨质疏松和(或)骨量减少的危险因素.方法 选取2007年收治的IBD患者69例(IBD组,其中CD 49例、UC 20例)以及年龄、性别相匹配的20名体检健康人群(对照组)为研究对象,根据CD活动指数(AI)以及Truelove-Witts评分判定疾病活动度,酶联免疫分析法检测骨钙素(OC)、25-羟维生索D3[25-(OH)D3] 、Ⅰ型胶原交联氨基末端肽(NTX)等骨代谢相关指标水平,测定骨密度(BMD)及体重指数(BMI).结果 IBD组25-(OH)D3水平[CD:(44.45±39.38)nmol/L、UC:(34.67±23.79)nmol/L] 较对照组[(98.42±25.84)nmol/L] 显著降低(P<0.05),NTX水平则显著升高[CD:(58.41±15.15)nmol BCE/mmol肌酐值、UC:(57.67±10.75)nmol BCE/mmol肌酐值、对照:(30.38±13.35)nmol BCE/mmol肌酐值,P<0.01] .使用皮质类同醇激素者OC和25-(OH)D3水平[分别为(17.31±13.43)ng/ml和(26.99±9.12)nmol/L] 较未使用皮质类固醇激素者[分别为(27.33±16.86)ng/ml和(45.33±39.03)nmol/L] 显著降低(P<0.05).根据BMD检测结果,CD组和UC组骨质疏松发病率分别为7/49(14.3%)和3/20,骨量减少发病率分别为19/49(38.8%)和7/20,两组间差异均无统计学意义(P>0.05).使用皮质类固醇激素者腰椎T值(-1.19±0.93)较未使用者(-0.80±1.29)显著降低(P<0.05),股骨颈T值两组间差异无统计学意义(P>0.05).高龄和低BMI是CD患者发生骨质疏松和(或)骨量减少的危险因素.结论 IBD患者BMD显著降低,易发生骨质疏松,高龄和低BMI是CD患者发生骨质疏松和(或)骨量减少的危险因素.25-(OH)D3、NTX对评价IBD患者骨代谢状况有一定价值.     

Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men

OBJECTIVE: Androgen replacement has been reported to increase bone mineral density (BMD) in hypogonadal men. We studied the effects of 6 months of treatment with a new transdermal testosterone (T) gel preparation on bone turnover markers and BMD. DESIGN: This was a prospective, randomized, multicentre, parallel clinical trial where 227 hypogonadal men, mean age 51 years (range: 19-68 years) were studied in 16 academic and research institutions in the USA. Subjects were randomized to apply 1% T gel containing 50 or 100 mg T (delivering approximately 5-10 mg T/day) or two T patches (delivering 5 mg T/day) transdermally for 90 days. At day 91, depending on the serum T concentration, the T gel dose was adjusted upward or downward to 75 mg T/day until day 180. No dose adjustment occurred in the T patch group. MEASUREMENTS: Serum T, free T and oestradiol, bone turnover markers and BMD were measured on days 0, 30, 90 and 180 before and after treatment. RESULTS: Application of T gel 100 mg/day resulted in serum T concentrations 1.4 and 1.9-fold higher than in the T gel 50 mg/day and the T patch groups, respectively. Proportional increases occurred in serum oestradiol. Urine N-telopeptide/creatinine ratio, a marker for bone resorption, decreased significantly (P = 0.0019) only in the T gel 100 mg/day group. Serum bone osteoblastic activity markers (osteocalcin, procollagen and skeletal alkaline phosphatase) increased significantly during the first 90 days of treatment without intergroup differences but declined to baseline thereafter. BMD increased significantly both in the hip (+1.1 +/- 0.3%) and spine (+2.2 +/- 0.5%) only in the T gel 100 mg/day group (P = 0.0001). CONCLUSIONS: Transdermal testosterone gel application for 6 months decreased bone resorption markers and increased osteoblastic activity markers for a short period, which resulted in a small but significant increase in BMD. Ongoing long-term studies should answer whether the observed increases in BMD are sustained or continue to be dependent on the dose of testosterone administered.