Bone turnover and hormonal perturbations in patients with fibromyalgia

OBJECTIVE: Studies of bone turnover in fibromyalgia (FM) have, to date, shown conflicting results. Although most patients with FM are women, only a few investigations have paid attention to the changes of sex hormones in FM. Moreover, FM is often viewed as a stress related disorder, and abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis have been found in FM. The aim of the study was to assess bone turnover using serum osteocalcin and CTx in patients with FM and study correlation between bone turnover parameters and parathormon and hormones of the HPA axis. METHODS: A total of 81 subjects participated in this study: 41 healthy volunteers and 40 patients with FM. Serum osteocalcin, crosslaps (C-telopeptide: CTx), parathyroid hormone (PTH), testosterone, estrogen, prolactin, FSH, and LH were measured. The mean age of the study population was 49.5 (7.6) years (32-69) and the mean disease duration was 8.1 (12.0) years (4.5-30.7). RESULTS: No difference between patients and controls were observed in serum calcium, phosphorus, creatinine, albumin, osteocalcin, testosterone, and urinary calcium. Patients had lower serum levels of CTx, estrogen, PTH and prolactin than controls and higher serum levels of LH and FSH with a significant statistical difference. No significant statistical correlation was observed between intensity of pain and fatigue and bone turnover parameters and PTH or hormones of the HPA axis. CONCLUSION: Our study showed that patients with FM had low bone resorption and normal bone formation compared to a control group. This was not related to several hormonal perturbations observed in these patients and may reflect functional impairment as suggested in previous studies.     

Bone turnover markers, anterior pituitary and gonadal hormones, and bone mass evaluation using quantitative computed tomography in ankylosing spondylitis

The objective of this study was to determine bone mineral density (BMD) distribution in ankylosing spondylitis (AS) using quantitative computed tomography (QCT), to study bone turnover and anterior pituitary and gonadal hormonal axis in AS, and to look for correlations between BMD, bone remodeling markers and gonadal and anterior pituitary hormones. Forty-three male consecutive patients with AS were enrolled prospectively [mean (SD) age of 36.4 (11.3) years (range: 17–67) and mean disease duration of 6.8 (5.2) years (range: 0.4–19)]. Spine BMD was measured in all patients by QCT, and the results were compared to 29 male patients undergoing lumbar CT scan for sciatica. Bone turnover and anterior pituitary and gonadal axis were assessed in 29 patients, and the results were compared to 30 male healthy blood donors. The mean (SD) BMD was 127.7 mg/cm³ (48.9) (range: 8.8–265.7) and 152.1 (25.3) (range: 34.2–190.4) in patients and controls, respectively (p=0.018). Patients had lower serum levels of osteocalcin and higher levels of serum testosterone, luteinizing hormone (LH), and prolactin than controls with a significant statistical difference. There was a positive significant statistical correlation between BMD and chest expansion, Schobers test, C7-wall distance, and negative significant statistical correlation with age, disease duration, Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Radiology Index (BASRI), and serum prolactin. No correlation was observed between bone turnover parameters and AS symptomatic and structural severity indexes. BMD is lower with increasing age and late and severe disease. Decreased bone formation with normal resorption and increased levels of serum prolactin may be involved in its pathophysiology.     

IS TESTICULAR ENDOCRINE FUNCTION ABNORMAL IN YOUNG MEN WITH SPINAL CORD INJURIES?

Plasma concentrations of FSH, LH, testosterone and prolactin have been studied in seventeen men, aged 19 to 38 years, with traumatic paraplegia. Plasma testosterone, FSH and LH values were normal in all patients. The median LH concentration in patients was significantly higher (P < 0.05) than in controls but there was no difference for FSH or testosterone. Plasma prolactin was high in five patients and the median prolactin concentration in patients was significantly greater (P < 0.001) than in controls. It is concluded that there is no evidence of primary testicular failure in young paraplegics but it is possible that testicular hypofunction in some paraplegics may be related to increased prolactin production.     

Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal

Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2) vit D], urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio, and urinary calcium (24 h collection) were measured (single-batch analysis) at study entry and after IGF-I normalization, along with sera from 32 age- and sex-matched controls. Compared with controls, PIIINP, OC, and CTx were significantly elevated in patients at baseline. Pegvisomant-induced serum IGF-I normalization (699 +/- 76 to 242 +/- 28 micro g/liter, P < 0.001) was associated with a significant decrease in PIIINP, markers of bone formation (type I procollagen amino-terminal propeptide, OC, and bone-related alkaline phosphatase), and resorption (CTx and urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio). 1,25-(OH)(2) vit D decreased and intact PTH increased significantly, but 25-hydroxy vitamin D was unaffected. A significant decline in calculated calcium clearance was observed. The decrease in serum IGF-I correlated positively with the decrease of serum PIIINP (r = 0.7, P < 0.01). After normalization of serum IGF-I, there was no statistical difference between patients and controls for any parameters for which control data were available. In conclusion, GH excess is associated with increased bone and soft tissue turnover. Pegvisomant-induced normalization of serum IGF-I results in a decrease in markers of bone and soft tissue turnover to levels observed in age-matched controls, and these changes are accompanied by an increase in PTH and a decrease in 1,25-(OH)(2) vit D. These data provide further evidence of the effectiveness of pegvisomant in normalizing the altered biological effects of GH hypersecretion.     

Type 2 diabetes mellitus is associated with increased axial bone density in men and women from the Hertfordshire Cohort Study: evidence for an indirect effect of insulin resistance?

Aims/hypothesis Previous studies have suggested that the high bone density often observed in type 2 diabetic patients may be explained by insulin resistance. We explored this hypothesis in the Hertfordshire Cohort Study.Methods A total of 465 men and 444 women aged 59 to 71 years and with no prior diagnosis of diabetes attended a clinic where a glucose tolerance test was performed and bone density measured at the femoral neck and lumbar spine. Biochemical markers of bone turnover (serum osteocalcin and urinary mean c-terminal cross-linking telopeptide of type II collagen) were measured in 163 men.Results According to WHO criteria, 83 men and 134 women were diagnosed with impaired glucose tolerance and a further 33 men and 32 women were diagnosed as having type 2 diabetes. Bone density was higher in newly diagnosed diabetic subjects, with relationships stronger in women (p<0.001) than men (p<0.05) and attenuated by adjustment for body mass index. In both sexes, we observed positive correlations between the total femur and femoral neck bone mineral density with measures of insulin resistance (r=0.17–0.22), with stronger results observed in women. These relationships did not apply after adjustment for body mass index. Glucose status did not lead to differences in osteocalcin level or c-terminal cross-linking telopeptide of type II collagen levels.Conclusions/interpretation Our findings suggest that hyperinsulinaemia may affect bone mineral density through indirect effects, e.g. body weight.     

老年男性骨密度的增龄改变与骨代谢有关激素的相关性研究

目的探讨老年男性增龄与骨密度(BMD)及骨代谢有关激素的关系。方法123例老年男性按年龄分成3组,分别测定骨密度及血清甲状旁腺素(PTH)、睾酮(T)、雌二醇(E2)、卵泡刺激素(FSH)、黄体生成素(LH)并进行比较。结果老年男性BMD随增龄而减少,在股骨近端和髋关节处更为明显(P<0.05),在腰椎不确定;老年男性T、E2处于低水平,而FSH、LH及PTH随增龄而增高,FSH更为明显(P<0.05)。结论随着增龄,老年男性MBD下降,T、E2水平低下,而FSH、LH和PTH水平增高。提示体内骨代谢有关激素的变化,可能是老年男性骨质疏松症发病的重要机制之一。     

Bone density in women with prolactinoma treated with dopamine agonists

Objectives (1) to evaluate bone density in women with prolactinoma treated with dopamine agonists and healthy controls, using dual energy x-ray absorptiometry (DXA), (2) to classify the results according to the current International Society for Clinical Densitometry (ISCD) criteria, and (3) to correlate bone density with lean and fat masses, biochemical data and clinical aspects of prolactinomas. Materials and methods A cross-sectional study was performed in two University referral centers. Forty-five premenopausal women with prolactinoma were submitted to DXA and blood analysis (prolactin, estradiol, testosterone, SHBG, calcium, phosphorus, PTH, C-telopeptides of type 1 collagen, and osteocalcin) by the time of their clinical evaluation. They were compared with 25 control women of similar age and body mass index distribution. Results Women with prolactinoma had lower lumbar spine Z-score than controls. Femoral neck, trochanter, and total proximal femur Z-scores were similar in patients and controls. Twenty-two percent of the patients had Z-scores below the expected age range vs. 4% in the control group. Lumbar spine, femoral neck, and total proximal femur Z-scores were mainly correlated with the amenorrhea duration. The trochanter Z-score was associated with the gynoid lean/fat mass ratio. Conclusions Based on the current ISCD criteria, bone density evaluation in women with prolactinoma reveals bone loss, especially of trabecular type. Bone density in these patients was particularly associated with the duration of amenorrhea, which reinforces the importance of the adequate disease control in women with prolactinoma in order to avoid complications of this disease.     

Bone Mineralization in Young Patients with Type 1 Diabetes Mellitus and Screening-identified Evidence of Celiac Disease

The aims of this study were to evaluate bone mineral density (BMD) and bone turnover markers in patients with type 1 diabetes and screening-identified evidence of celiac disease, i.e., celiac autoimmunity. We screened 50 consecutive type 1 diabetic patients for IgA antitissue transglutaminase to identify those with celiac autoimmunity. Eight seropositive patients were identified on this screening, and 12 patients matched for gender and age range were selected as a control group from among the type 1 diabetic patients without celiac autoimmunity. Patients and controls underwent dual-energy X-ray absorptiometry (DEXA) for measurement of bone mineral status and had their blood levels of osteocalcin, carboxy-terminal telopeptide of type I collagen (CTX), calcium, and phosphorus determined. BMD was further adjusted for height, weight, and pubertal stage. Radiographic and blood markers of bone mineralization were compared between patients and controls. BMD (Z-score) at the lumbar spine was −1.44 ± 0.5 SD for patients and 0.04 ± 0.2 SD for controls (P = 0.02). Bone mineral content was 37.9 ± 4.5 g for patients and 49.4 ± 2.6 g for controls (P = 0.049). Adjusted BMD was −0.62 ± 0.5 SD for patients and 0.81 ± 0.09 SD for controls (P = 0.04). After adjustment, four patients and none of the controls presented BMD < −1 SD (P = 0.01). Osteocalcin, CTX, calcium, and phosphorus blood levels were not significantly different between patients and controls. Celiac autoimmunity is associated with reduced bone mineralization in type 1 diabetic patients. The pathophysiological mechanisms and clinical relevance of this finding remain to be further investigated.     

EFFECTS OF ETHINYLOESTRADIOL ON PLASMA LEVELS OF PITUITARY GONADOTROPHINS, TESTICULAR STERIODS AND SEX HORMONE BINDING GLOBULIN IN NORMAL MEN

Daily measurements of plasma FSH, LH, prolactin, testosterone, 17β-oestradiol and sex hormone binding globulin (SHBG) activity were made in eight healthy, normal men during treatment with oral ethinyloestradiol (EE₂) in a dose of 30 μg/day for 5 days following a 5-day control period. No significant changes in plasma levels of FSH and prolactin during oestrogen treatment occurred. In contrast, plasma concentrations of both LH and testosterone showed a biphasic pattern. Following an initial suppression during the first 3 days of oestrogen treatment both LH and testosterone increased again to baseline values despite continuation of oestrogen administration. The secondary rise of both hormones was associated with (and probably resulted from) a nearly 100% increase in the plasma concentration of SHBG binding activity, and hence reduction of free testosterone index (FTI). Unlike testosterone, plasma 17β-oestradiol during EE₂ administration did not show a biphasic pattern, but a progressive decline that was positively correlated with the fall in FTI. The rapidity of onset and magnitude of the observed rise in SHBG levels emphasizes the need for measurement of this binding protein (or the free testosterone fraction) in studies on feedback regulation of gonadotrophins employing exogenous EE₂ in human males. The observed increase of SHBG to supraphysiological values suggests that currently employed EE₂ doses in such studies may be less ‘physiologic’ than is often assumed.     

Sex hormones and calcium regulating hormones in rheumatoid arthritis

Rheumatoid arthritis (RA) occurred frequently in women. Exogenous estrogen has been reported to alleviate the symptoms of patients with RA. But the implications of sex hormones and immunological abnormalities in RA remain to be elucidated. Therefore, we measured sex hormones (LH, FSH, estradiol, testosterone and prolactin), bone metabolic markers (midregion and carboxy terminal mainly recognized PTH1-84, intact PTH1-84, bone GLA protein and alkaline phosphatase), bone mineral, in lumbal bone with quantitative tomography (QCT) and with of cortex with microdensitometry in 52 females with RA and 46 females with osteoarthritis (OA) as a control group. Sex hormones and bone metabolic markers were analyzed as independent variables of serum LH, FSH and estradiol levels, using one way analysis, in patients with RA and OA. The more increased serum FSH and LH levels were, the more decreased serum estradiol levels were in both RA and OA groups, when they were considered as independent variables. These results indicate that the secretory function of pituitary and ovary axis hormones are normally enacted in RA. On the other hand, when the sex hormones of the patients under 53 years of age were studied in both groups, serum FSH adn LH showed significantly higher levels, while serum estradiol levels revealed decreased tendency in RA, compared with these in RA. Thus the pituitary ovary secretory function in patients with RA was suggested to be disturbed in early stage of age, indicating that the sex hormones would be partly implicated in calcium and bone metabolism in patients with RA.     

Peptide and steroid hormone levels in pre- and postmenopausal breast carcinoma

Circulating levels of LH, FSH, prolactin, estradiol, progesterone and testosterone were measured by radioimmunoassay in 15 premenopausal (PR-M) age matched healthy controls, 35 premenopausal breast cancer patients prior to therapy, 20 postmenopausal (PO-M) age matched healthy controls and 68-71 postmenopausal breast cancer patients prior to therapy. The patients had histologically proven breast cancer. In PR-M breast cancer group, the LH and progesterone did not differ significantly whereas prolactin showed marked elevation (p less than 0.001) and estradiol and testosterone showed significant decrease (p less than 0.001). The PO-M breast cancer patients exhibited remarkable increase in the levels of LH, FSH, prolactin and testosterone (p less than 0.001) whereas estradiol and progesterone showed little increase in the levels (p less than 0.2 and less than 0.1, respectively). From the results, it is concluded that prolactin and altered ratio of estrogen and androgen plays a major role in the genesis of breast cancer.     

PLASMA TESTOSTERONE AND PROLACTIN IN THE MENSTRUAL CYCLE

Daily hormonal studies during nine ovulatory menstrual cycles showed that plasma prolactin and testosterone concentrations fluctuated randomly and independently. Mean plasma testosterone levels were found to be higher during the 7 days before and after the mid-cycle LH peak when compared to the premenstrual phase (P less than 0-01). No correlation was found between daily levels of prolactin and those of LH, FSH, oestrogen or progesterone and no correlation was seen between peaks of prolactin and testosterone or mean prolactin and testosterone levels. The lack of correlation between blood levels of prolactin and testosterone during the menstrual cycle suggests that prolactin is unlikely to have any direct controlling influence on the cyclical nature of testosterone production observed during ovulatory menstrual cycles.     

A paradigm of integrative physiology, the crosstalk between bone and energy metabolisms

Thanks to integrative physiology, new relationships between organs and homeostatic functions have emerged. This approach to physiology based on a whole organism approach has allowed the bone field to make fundamental progress.In the last decade, clinical observations and scientific evidences in vivo have uncovered that fat with leptin controls bone mass through brain including a hypothalamic relay and sympathetic nervous system.The finding that energy metabolism affects bone remodelling suggested that in an endocrine perspective, a feedback loop should exist. Beside its classical functions, bone can now be considered as a true endocrine organ secreting osteocalcin, a hormone pharmacologically active on glucose and fat metabolism. Indeed osteocalcin stimulates insulin secretion and β-cell proliferation. Simultaneously, osteocalcin acts on adipocytes to induce Adiponectin which secondarily reduce insulin resistance. This cross regulation between bone and energy metabolism offers novel therapeutic targets in type 2 diabetes and osteoporosis.     

Influence of diabetes on the gonadotropin response to the negative feedback effect of testosterone and hypothalamic neurotransmitter turnover in adult male rats.

The influence of diabetes on the gonadotropin response to the negative feedback effect of testosterone (T) and hypothalamic neurotransmitter turnover rates in adult male rats was evaluated. Adult male Sprague-Dawley rats were made diabetic by an intraperitoneal injection of streptozotocin (STZ; 5 mg/100 g body weight) in citrate buffer. Vehicle-injected rats served as controls. On day 9, all rats were bilaterally castrated and treated subcutaneously on alternate days with either peanut oil or T propionate (TP) in peanut oil (100 micrograms/rat). Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and T concentrations were measured by specific radioimmunoassays from blood samples collected on day 1 (before castration) and 2, 4, 6, and 7 days after castration. On day 7 after castration (day 15 after vehicle or STZ treatment), 1 h before autopsy, the rats were injected intraperitoneally with saline or a tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (25 mg/100 g BW), for the measurement of norepinephrine (NE) and dopamine turnover in median eminence and medial basal hypothalamus (MBH). Circulating FSH, LH, PRL, and T levels were significantly lower (FSH and T: p less than 0.001; LH and PRL: p less than 0.05) in gonad-intact rats treated with STZ than in vehicle-injected animals. The castration-induced increase in plasma LH levels was attenuated in diabetic rats. The suppressive effect of T on LH secretion was significantly greater (p less than 0.001) in STZ-treated rats relative to TP-treated nondiabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute effects of a single session of aerobic exercise with or without weight-lifting on bone turnover in healthy young women

This study aimed to investigate the acute effects of exercise on bone turnover and to determine whether brisk walking with or without weight-lifting makes a difference on bone metabolism. Nine healthy women performed two exercise bouts: brisk walking on a treadmill for 30 min (E), and similar exercise carrying 5 kg of weight in a backpack (WE). Serum parathyroid hormone (PTH), osteocalcin (OC), calcitonin (CT), procollagen type 1 carboxy terminal propeptide (PICP), procollagen type 1 amino terminal propeptide (PINP), type 1 collagen carboxy terminal telopeptide (ICTP), total alkaline phosphatase (ALP), and urine deoxypyridinoline (D-Pyr) levels were studied. Resting values served as control. Significant variances were observed only in serum ALP and PTH values. Variances in ALP values within subjects after exercise were statistically significant (analysis of variance in repeated measurements [AVRM], P = 0.000). E caused a significant decrease, while WE caused a significant increase in ALP values at the 24th h (Bonferroni pairwise comparisons tests [BPC t-test]: P = 0.028, P = 0.000, respectively). Variances in PTH values within subjects after exercise were statistically significant (AVRM, P = 0.029), while diurnal variation was not significant (P = 0.981). E caused significant alterations in PTH levels (an increase at the 30th min, turned towards baseline at the 45th min) (BPC t-test, P = 0.007). WE also caused alterations in PTH levels, though insignificant (BPC t-test, P = 1.00). Brisk walking for 30 min has stimulating effects on bone turnover by various mechanisms without any additive effect of weight bearing.     

Biochemical markers and bone mineral density in patients with hip fractures in men

The purpose of this study was to determine whether males with hip fractures have associated decreased gonadal function. Second void urine and serum samples were obtained from 25 male hip fracture patients (mean age+/-SD, 78.5+/-5.9 years) and 19 age- and gender-matched controls (77.6+/-6.2 years). Serum levels of luteinizing hormone (LH), total testosterone (Te), total estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), 1,25(OH)2D3, N-mid osteocalcin (OC(N-mid)), type I collagen degradation products (S-CTx) and urinary levels of pyridinoline (Pyr), deoxypyridinoline (Dpyr) and type I collagen degradation products (U-CTx) were measured. Bone mineral density (BMD) of the L2-4 spine, femoral neck, trochanter, Ward's triangle, distal one third portion of the radius and ultradistal radius were also measured in the fracture group. Serum levels of LH, E2, Te, DHEAS, 1,25(OH)2D3 and OCN-mid in the fracture group were not statistically different from those in the control group. Levels of urinary Pyr, CTx and S-CTx in the fracture group increased significantly compared with those in the control group. In the fracture group, serum levels of Te correlated positively with distal one third portion of the radius BMD and ultradistal radius BMD. U-CTx and S-CTx correlated negatively with all the BMD measurement sites in the hip region and with the radius BMD. An imbalance between bone resorption and bone formation was evident in male hip fracture patients. However, male patients with hip fractures did not show associated decreased gonadal function in this study.     

Effect of renal transplantation on pituitary gonadal function.

Twelve adult male patients who had undergone successful renal transplantation were investigated. The gonadotropin responses to 100 microgram luteinizing hormone-releasing hormone (LRH) were studied, and basal serum testosterone and prolactin assayed. Significantly elevated mean basal levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were found, associated with a correspondingly excessive LH and FSH response to LRH. Mean basal serum testosterone levels in the posttransplant patients were significantly lower than in normal controls, while the mean basal prolactin levels were similar in the two groups. The results were not influenced by the varying degrees of renal function found in the posttransplant patients.     

Endocrine status in stage II vs. advanced premenopausal and postmenopausal breast cancer patients.

Circulating preoperative levels of DHEA-S, androstenedione and SHBG were measured in 40 premenopausal and 49 postmenopausal breast cancer patients, and in 30 and 15 age-matched healthy controls, respectively. Moreover, the levels of LH, FSH, prolactin, estradiol, progesterone, testosterone, DHEA-S, androstenedione and SHBG of Stage II breast cancer patients were compared with advanced patients and also with controls. In premenopausal patients the levels of steroid hormones were significantly low whereas those of peptide hormones were significantly high. On the contrary, in postmenopausal patients, except DHEA-S, all other hormones were significantly elevated in comparison with controls. In premenopausal patients, DHEA-S, androstenedione, estradiol, progesterone, and testosterone decreased as stage advanced with concomitant increase of SHBG, LH, FSH and prolactin when compared with hormone levels of Stage II patients. In postmenopausal advanced breast cancer patients, when compared with Stage II patients, the levels of SHBG, LH, FSH, and prolactin increased significantly, while DHEA-S, androstenedione, estradiol, and progesterone decreased as stage advanced.     

Choosing an oestrogen replacement therapy in young adult women with Turner syndrome

OBJECTIVE Hormone replacement therapy (HRT) is prescribed to most patients with Turner syndrome (TS) although its use in adult TS patients has not been scientifically evaluated. The present study was performed to compare the short‐term effects in adult women with Turner syndrome of low‐dose oral conjugated oestrogen (0·625 mg, CE) with relatively high dose ethinyl oestradiol (30 µg, EE2); both combined with an oral progestin. DESIGN and PATIENTS After 4 months off HRT, 17 young, otherwise healthy women with TS were enrolled in a random, unblinded, crossover study of the two oestrogenic preparations, each given for 6 months. MEASUREMENTS We compared parameters of oestrogenic activity that would cover immediate changes in hormone levels, biochemistry, bone turnover, uterine and cardiac variables, which constitute risk factors for later development of diabetes, atherosclerosis, osteoporosis and aortic dissection. RESULTS Serum FSH returned to normal follicular phase levels only on the EE2 regimen. The hypotrophic endometria normalized with either of the two oestrogen regimens with no excessive hypertrophy. Hyperinsulinaemia was suppressed to normal by both EE2 and CE. PTH and 1,25‐dihydroxyvitamin D levels increased on HRT (EE2 > CE), and phosphorus decreased. Alkaline phosphatase, osteocalcin and urinary deoxypyridinoline cross‐links (DPD) were high off therapy; the former two suppressed to high–normal levels on the EE2 regimen, but not on CE, and DPD did not normalize with either HRT. Lipid profiles in these young TS patients were normal. Liver enzymes were mildly elevated off therapy and suppressed to normal levels on both regimens, but more so with EE2. CONCLUSIONS The risk factors embodied in hyperinsulinaemia and enhanced bone turnover which, ultimately, have consequences for TS morbidity, are minimized by HRT. In the short term, neither regimen is effective for bone turnover in adult women with Turner syndrome.     

Acute changes of bone turnover and PTH induced by insulin and glucose: euglycemic and hypoglycemic hyperinsulinemic clamp studies

Bone turnover is acutely suppressed after feeding or oral glucose. Insulin infusion suppresses bone turnover and might mediate this effect, but this is confounded by a possible direct effect of hypoglycemia. We examined the effect of euglycemic hyperinsulinemia and hypoglycemic hyperinsulinemia on bone turnover using an insulin clamp. Sixteen men participated in this double-blind crossover study. Clamp induction involved infusion of insulin (80 mU/m(2).min) while maintaining euglycemia (5 mmol/liter) for 40 min with a variable rate dextrose infusion. Glucose was lowered to 2.5 mmol/liter (hypoglycemic clamp) or maintained at 5 mmol/liter (euglycemic clamp) for a further 105 min. Nine controls received a matched saline infusion. Measurements included serum C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide, osteocalcin, and PTH. Induction of hyperinsulinemia resulted in a reduction in PTH (27% +/- 5; P < 0.01), but no significant change in bone turnover from baseline. Hypoglycemic clamp resulted in suppression of serum C-terminal telopeptide of type I collagen by 34% +/- 3, procollagen type I N-terminal propeptide by 15% +/- 1, osteocalcin by 5% +/- 1, and PTH by a further 12% +/- 5 (all P < 0.05). By contrast, there was no significant change in any marker of bone turnover during euglycemic clamp. Postprandial hyperinsulinemia is unlikely to explain the acute suppression of bone turnover with feeding. The reduction in bone turnover during hypoglycemia may be related to hypoglycemia itself, acute changes in PTH, or other hormones released in response to hypoglycemia.