Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes

Aims To determine the prevalence and biochemical/hormonal determinants of osteopenia and osteoporosis in adults with Type 1 diabetes. Methods One hundred and two patients (52 female, 50 male) with Type 1 diabetes aged 20–71 years underwent cross‐sectional assessment of biochemical/hormonal markers of bone metabolism, and bone mineral density (BMD) measurement at forearm, hip and spine using dual energy x‐ray absorptiometry. BMD data were available for 102 age‐ and gender‐matched population‐based control subjects. Results After adjusting for age and body mass index (BMI), osteopenia and osteoporosis were more common at the spine in males with Type 1 diabetes than in control subjects (P = 0.030). In Type 1 males, after adjustment for age and BMI, BMD, T‐ and Z‐scores at the hip, femoral neck and spine were lower compared with age‐matched control subjects (P ≤ 0.048). Female Type 1 patients and control subjects had similar BMDs and T‐ and Z‐scores at all sites. On multiple linear regression analysis, which adjusted for the natural logarithm of the sex hormone binding globulin concentration, smoking status and alcohol consumption, and (for women) menopausal status, each of BMI, serum ionized calcium and serum alkaline phosphatase (negatively) were independently associated with BMD at the hip and femoral neck in Type 1 diabetic subjects. Conclusions Adult males with Type 1 diabetes have reduced bone density at the hip, femoral neck and spine when compared with age‐matched control subjects. Impaired bone formation may occur in Type 1 diabetes.     

Proximal femur density in type 1 and 2 diabetic patients.

This study reports on the proximal femur mineral content in 36 Type 1 and 60 Type 2 diabetic patients. Bone mass measurements were performed in the neck, Ward's triangle and in the trochanteric area of the femur, using dual-photon absorptiometry with 153Gd. Bone mineral density (BMD) was significantly decreased in Type 1 diabetic men and women as well in Type 2 men, when compared with a non diabetic matched population. In Type 1 men, neck and Ward's triangle densities were reduced from 0.94 +/- 0.05 to 0.86 +/- 0.11 (p = 0.007) and from 0.87 +/- 0.10 to 0.74 +/- 0.14 g.cm-2 (p = 0.011), respectively. In Type 1 women, BMD was reduced from 0.97 +/- 0.10 to 0.90 +/- 0.10 g.cm-2 (p = 0.023) in the femoral neck. In Type 2 men, BMD in Ward's triangle was also significantly lower than in controls: 0.69 +/- 0.14 vs 0.76 +/- 0.19 g.cm-2, respectively (p = 0.001). In contrast, no bone loss was observed in a group of Type 2 overweight diabetic women. No statistical correlation was observed between bone loss and age, duration of diabetes, body mass index, C-peptide levels, daily insulin doses, HbA1 and the presence of diabetic complications. In conclusion, long-standing Type 1 diabetic men and women and Type 2 diabetic men have a decrease in the proximal femur bone mass. Type 2 diabetic women appear to be protected from diabetic osteopenia.     

Bone mineral density of both genders in Type 1 diabetes according to bone composition

AIMS: This study is an investigation of the impact of Type 1 diabetes on bone mineral density (BMD) with regard to bone composition. MATERIAL AND METHODS: Thirty male and 30 premenopausal female patients with Type 1 diabetes (IDD) were retrospectively compared with an equal number of healthy individuals, matched on a person-to-person basis and to the reference population mean. BMD was measured at the L2-L4 vertebrae and femoral neck (FN) by dual energy X-ray absorptiometry (DXA). RESULTS: BMD absolute values were significantly lower in the diabetic than in the healthy males at vertebrae and FN (P<.05). The vertebral BMD values of diabetic women did not significantly differ, whereas those of FN were significantly lower compared with those of the healthy participants. FN age-adjusted BMD values (Z scores) were significantly lower than those of the healthy persons and the population reference mean in both genders (P=.01, <.001 for males and <.01 for females), whereas regarding the vertebrae, only in the diabetic males (P<.05 and <.01 respectively). The percentages of osteopenia and osteoporosis were significantly higher in the male compared to the female diabetic patients (P<.001). No significant correlations existed between the BMD values and diabetes duration, glycosylated hemoglobin (HbA1c) concentration, or age of diabetes onset. Similar results were obtained when applying stepwise multiple regression analysis to explain the BMD value variance. CONCLUSIONS: Young males with Type 1 diabetes exhibit significantly lower BMD values of trabecular and mixed cortical-trabecular bone, compared with matched healthy persons. Premenopausal females with Type 1 diabetes present significantly lower BMD values of mixed bone only. Blood glucose control and diabetes duration do not appear to influence BMD behavior.     

Osteopenia in insulin-dependent diabetes mellitus; prevalence and aspects of pathophysiology

The objective was to evaluate the prevalence and severity of osteopenia in patients with uncomplicated insulin-dependent diabetes mellitus (IDDM) and to obtain more information on the pathophysiology of diabetic osteopenia. In 35 patients with uncomplicated IDDM (21 men and 14 women; age 37.6+/-9.9 yr; duration of disease 8.5+/-3.5 years) bone mineral density was measured by dual energy X-ray absorptiometry (DEXA). In addition, markers of bone formation [plasma insulin-like growth factor I (IGF-I), serum alkaline phosphatase (ALP), serum bone alkaline phosphatase (BAP) and serum osteocalcin] and bone resorption [urinary excretion of calcium and of the cross-linked N-telopeptide of type 1 collagen, both corrected for the excretion of creatinine] were measured in the diabetic patients and in 33 healthy controls, matched for sex, age, height, weight and body mass index (BMI). In 67% of the diabetic men and 57% of the diabetic women osteopenia of the femoral neck and/or the lumbar spine (T-value < or = -1 SD) was present. Fourteen percent of the male patients, but none of the female patients, met the criteria for osteoporosis (T-value < or = -2.5 SD). In the whole group of diabetic patients the mean plasma IGF-I level tended to be lower (p<0.10) as compared to that in the controls. In the diabetic patients with femoral neck osteopenia, the mean plasma IGF-I level was significantly lower (p<0.05) than in those without osteopenia at this site. There were no differences in the mean serum ALP, BAP and osteocalcin levels between the diabetic patients and the controls, nor between the diabetic patients with and without femoral neck osteopenia. Considering only the male diabetic patients, significantly lower mean plasma IGF-I (-26%), serum ALP (-24%) and serum osteocalcin (-38%) levels were present in the patients with femoral neck osteopenia than in those without osteopenia at this site, suggesting lowered bone formation. The bone resorption markers were similar in all (sub)groups of diabetic patients and not different between diabetic patients and controls. Bone mineral density (BMD) did not correlate with plasma levels of glycosylated hemoglobin (HbA1c). BMD values were not related to any of the bone resorption or formation markers, except for plasma IGF-I both in the femoral neck (r=+0.38, p=0.026) and the lumbar spine (r=+0.34, p=0.043). Our data demonstrate that at least in male patients with IDDM, osteopenia is the consequence of a lowered bone formation with a predominance of bone resorption over formation.     

Serum osteocalcin levels in diabetes mellitus: analysis of the type of diabetes and microvascular complications

Summary Recent studies indicate that serum levels of osteocalcin, a 49-aminoacid bone matrix protein, are a biochemical marker of bone formation. In order to study bone metabolism in diabetes mellitus, in 28 patients with Type 1 (insulin-dependent) diabetes mellitus, in 38 patients with Type 2 (non-insulin-dependent) diabetes mellitus and two control groups, matched for Type 1 and Type 2 diabetic patients, respectively, serum levels of osteocalcin, parathyroid hormone and 25 hydroxy vitamin D were measured by radioimmunoassay. Whereas in Type 1 diabetic patients and control subjects serum levels of osteocalcin and 25 hydroxy vitamin D were not statistically different, serum osteocalcin and 25 hydroxy vitamin D levels were significantly decreased in Type 2 diabetic patients when compared with corresponding control subjects (p<0.03 and p<0.001, respectively). Independent of the type of diabetes, serum parathyroid hormone levels were comparable in diabetic patients and matched control subjects. Serum osteocalcin levels were significantly lower in Type 1 diabetic patients with retinopathy and/or proteinuria than in Type 1 diabetic patients without microangiopathy (p<0.05). Whereas serum parathyroid hormone levels in Type 2 diabetic patients with retinopathy and/or proteinuria were significantly increased (p<0.02), 25 hydroxy vitamin D levels were decreased (p<0.02) when compared with Type 2 diabetic patients without microangiopathy. Our data give evidence of a vitamin D deficiency and a decreased bone formation in patients with Type 2 diabetes mellitus. In Type 1 diabetes mellitus bone formation as reflected by serum osteocalcin levels is influenced by the presence or absence of microangiopathic complications.     

Bone mineral density, collagen type 1 α 1 genotypes and bone turnover in premenopausal women with diabetes mellitus

Summary Osteopenia is a recognised complication of diabetes mellitus which could be due to abnormal bone turnover or disturbances in the calcium/parathyroid hormone/vitamin D axis or both. Genetic factors also play an important part in determining bone mass although this has not been studied in diabetes. Recently a polymorphism of the collagen type 1 α 1 (COL1A1) gene has been shown to be associated with low bone mass in British women. To identify subjects with diabetes who may be at risk of developing osteoporosis and fractures, we analysed bone mineral density in relation to the biochemical markers of bone turnover, calcium homeostasis and the COL1A1 genotype in a group of premenopausal women with Type I (insulin-dependent) diabetes mellitus (n = 31), Type II (non-insulin dependent) diabetes mellitus (n = 21) and control subjects (n = 20). Bone mineral density was lower at the femoral neck in the subjects with Type I diabetes (p = 0.08) as were serum 25-hydroxyvitamin D compared with control subjects (p = 0.023) and this was negatively correlated with serum collagen type 1 C-terminal propeptide (r = –0.56, p < 0.001). Bone mineral density in Type II diabetes was not different from control subjects, after correction for body mass index. Bone resorption was, however, raised in the Type II diabetic subjects as reflected by the higher urinary deoxypyridinoline values (p = 0.016) and lower collagen type 1 C-terminal propeptide:deoxypyridinoline ratio (p = 0.04). In the whole group studied, subjects with the COL1A1 ’s' genotype had lower bone mineral density at the femoral neck (p = 0.01) which was partly attributable to a lower body mass index. Following multiple regression analysis body mass index and collagen type 1 C-terminal propeptide concentrations remained determinants of bone mass at all three sites, whereas genotype appeared to be a predictor of bone mass at the femoral neck only. We conclude that measurement of these variables could prove useful in firstly identifying those diabetic women at risk of osteoporosis and secondly guiding therapeutic intervention. [Diabetologia (1998) 41: 1314–1320] Received: 2nd March 1998 and in revised form: 27 April 1998     

糖尿病对骨密度及相关激素的影响

目的 观察DM患者骨密度（bone mineral density,BMD)及其相关激素的改变，并探讨其发生机制。方法 采用双能（线吸收法测量2型DM患者68例、1型DM患者54例和健康人62例的BMD，放免法测定血清骨钙素、降钙素和25羟维生素D3，免疫放射法测定血清完整甲状旁腺素及I型胶原羧基末段前肽。结果 ①两组DM患者全血HbA1c水平均显著高于对照组（P＜0．01），血清骨钙素水平显著低于对照组（P＜0．01）；②2型DM组BMI、大转子BMD显著高于对照组和1型DM组（BMI，P＜0．01；BMD，P＜0．05）；1型DM组股骨颈BMD低于对照组和2型DM组（P＜0．05），经BMI纠正后，1型DM组股骨颈BMD仍低于对照组（P＜0．05）；③1型DM组各位点BMD与血清I型胶原羧基末段前肽水平呈负相关（P＜0．05），2型DM组腰椎和大转子BMD与全血HbA1c水平呈负相关（P＜0．05）。结论 与健康人群相比，1型DM患者BMD明显降低，2型DM患者BMD明显增高，但经BMI纠正后，这种差异性消失；骨转化降低以及糖尿病代谢紊乱可能参与了糖尿病骨质疏松的发生。     

Bone mineral mass is associated with interleukin 1 receptor autoantigen and TNF-alpha gene polymorphisms in post-menopausal Mediterranean women

Bone mass is known to be under genetic control. Interleukin-1 (IL-1), interleukin-6 (IL-6) and TNF-alpha are strong inductors of bone resorption. The estrogenic deficiency that occurs during menopause leads to an increase in the production of these cytokines. We analyzed the genetic susceptibility of several polymorphisms of the interleukin-1 receptor antagonist (IL-1ra), IL-6 and TNF-alpha genes in lumbar spine and hip bone mass in a sample of post-menopausal Caucasian Mediterranean women with osteoporosis. 104 post-menopausal osteoporotic women (58.6+/-4.8 yr) and 51 post-menopausal women without osteoporosis as the control group (57.2+/-4.5 yr) were studied. The osteoporotic group was in turn sub-classified into severe and non-severe osteoporosis. The variable number of tandem repeats IL1-ra, IL-6 SfaNI and TNF-alpha NcoI genetic polymorphisms were studied. Biochemical markers of bone turnover were measured in blood and urine. Women carrying the A2 allele (A2+) of the IL-1ra gene showed greater BMD in the lumbar spine (p=0.02) and hip (p=0.006), compared to those not carrying the allele (A2-). The IL-6 polymorphism studied in its 5' flanking region did not show any association with BMD values. The TNF-alpha gene G allele was associated with a greater bone mass in the non-severe osteoporotic subgroup, both in the lumbar spine (p=0.0007) and in the hip (p=0.02). Likewise, genotype combination A2+GG was associated to a greater hip BMD at the femoral neck and Ward triangle levels (p=0.02). We conclude that both IL-1ra and TNF-alpha can be candidate loci to be studied in the susceptibility to develop post-menopausal osteoporosis.     

Whole body composition and regional bone mass in women with insulin-dependent diabetes mellitus

OBJECTIVE Reduced bone mass has been reported In adult patients with insulin-dependent diabetes mellitus but there are few data on bone density in the axial skeleton or on whole body composition In this group. The aim of this study was to determine whether whole body and regional bone mass are normal in middle-aged women with insulin-dependent diabetes mellitus. DESIGN Total and regional bone mass were measured In 24 post-menopausal women aged 43–69 years (mean 56·3) with insulin-dependent diabetes, recruited during routine clinic attendance. Results were compared with those obtained from 24 age and weight-matched community-based post-menopausal women. MEASUREMENTS Whole body bone mineral Content and bone mass in the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry on a Lunar DPX. RESULTS Whole body bone mineral content was significantly lower in the diabetic women than in community-based controls (P= 0·02). There was no significant difference between the two groups in whole body bone density or lumbar spine bone density. Mean bone density in the femur was lower in the patient group at all sites assessed (femoral trochanter P= 0·003, femoral neck, P= 0·057). Values for all regional bone density measurements in the diabetic women were within the Lunar reference range (mean ± 2 SD) and at all sites the mean value was close to 100% of the sex and age-matched reference value. There was no correlation between duration or control of diabetes and bone mass at any site. CONCLUSIONS Insulin-dependent diabetes mellitus In middle-aged women is associated with small reductions in total body bone mineral content and in femoral bone density; the clinical Significance of these findings in terms of subsequent fracture risk remains to be established. No evidence was found In this study for a reduction in whole body or lumbar spine bone density.     

A five-year prospective study of bone mineral density in men and women with diabetes: The Fremantle Diabetes Study

To examine longitudinally the effect of diabetes on bone structure and metabolism, we measured bone mineral density (BMD) and turnover markers in 26 type 1 (mean age 49 years) and 27 type 2 (mean age 65 years) diabetic patients without known osteoporosis from a community-based sample at baseline and 5 years later. In the 17 type 1 men, BMD fell at the femoral neck (0.804 ± 0.145 vs. 0.769 ± 0.129 g/cm²; P = 0.003) with no change at lumbar spine or forearm. In the 11 type 2 women, BMD decreased at all sites except spine (femoral neck 0.779 ± 0.119 vs. 0.742 ± 0.090 g/cm²; P = 0.019). BMD did not fall at any site in type 1 women or type 2 men. There was an increase in serum alkaline phosphatase and trend to higher serum beta carboxyl-terminal type I collagen telopeptide concentrations in the type 1 patients, and a decrease in free testosterone in the type 1 men. These data show that the rate of demineralization at the femoral neck in type 1 men is similar to that in older post-menopausal type 2 women. Changes in biochemical markers suggest that, in type 1 men, there is ineffective bone formation associated with accelerated bone resorption and lower sex steroid bioavailability. These findings may have implications for the clinical management of young male adults with diabetes.     

Type 2 diabetes mellitus and osteopenia: is there an association?

We report the results of bone mineral density (BMD) measurements in type 2 diabetic patients, in comparison to healthy controls. In this prospective study, a total of 277 subjects (aged 30–60 years) with type 2 diabetes mellitus, outpatients at the Cukurova Medical School Hospital, were evaluated for BMD at L₁–L₄ lumbar vertebrae and at the femur (neck, trochanter, Ward's triangle and total) by DEXA (dual energy X-ray absorptiometry). The patients' diabetes duration, treatment, glycemic control and chronic diabetic complications were recorded, and these data were evaluated for any relationship in respect to the BMD measurements. BMD results of the diabetic patients were compared with those of 262 healthy non-diabetic control subjects living in the same geographic region. BMD was found to be increased at the femoral neck among diabetic women and men aged 51–60 years. However, BMD values at lumbar regions of diabetic men where lower than control in all age group. There was no difference in values of BMD for both genders in the other regions. Type 2 diabetic patients may have lower, similar or higher BMD measurements at different ages and anatomic regions, so each patient should be evaluated individually. Further studies are needed to make a conclusion on this issue. Received: 18 October 2002 / Accepted in revised form: 2 April 2003 Correspondence to M. Sert     

Diabetes and premature menopause: is their co-existence detrimental to the skeleton?

OBJECTIVE: Premature menopause is a known risk factor for osteoporosis, whilst the influence of type 2 diabetes on bone mineral density (BMD) is still controversial. DESIGN AND METHODS: BMD values assessed by dual-energy X-ray absorptiometry (DXA) in L2-L4 vertebrae and the femoral neck (FN) of 40 diabetic women with premature menopause (D-EMP) were compared with those of 60 non-diabetic, prematurely menopausal women (EMP) and 60 diabetic women with normal menopause (D-NMP) who had been matched by age and body mass index (BMI). In all women, the time elapsed since menopause ranged between 10 and 25 years and the duration of diabetes exceeded 75% of the postmenopausal time period. The age of D-EMP women was 58.7+/-5 years (mean+/-1 s.d.), age at menopause 39.5+/-2.7, years since menopause 18.6+/-4.9, BMI 27.8+/-4.3 kg/m(2) and duration of diabetes 13.9+/-3.9 years. RESULTS: Vertebral BMD values of D-EMP women were significantly higher than those of EMP women (0.908+/-0.135 vs. 0.817+/-0.14 g/cm(2), P = 0.002), although there was no significant difference between D-EMP and D-NMP women (0.886+/-0.15 g/cm(2)). No significant differences were observed in FN BMD values between all groups. Age-adjusted BMD values (Z scores) of D-EMP women were higher than EMP women in both anatomic sites (P < 0.01), but did not differ from D-NMP women. In contrast to the other two groups, no statistically significant correlation was observed in D-EMP women between the BMD values of either anatomic area and the time elapsed since menopause. HbA(1c) values were positively correlated only to vertebral BMD values of the D-EMP group (P < 0.05). No correlation was observed between the BMD values and the duration of diabetes either in D-EMP or in D-NMP women. CONCLUSIONS: Type 2 diabetes seems to positively affect the mineral density of the trabecular bone in women with premature menopause. The duration of diabetes does not appear to influence bone mass.     

Low serum concentrations of insulin-like growth factor I are associated with femoral bone loss in a population-based sample of postmenopausal women

OBJECTIVE: Cross-sectional studies suggest that the decline in insulin-like growth factor-I (IGF-1) levels with age may contribute to age-associated bone loss. However, prospective data on the relation between circulating IGF-I and bone loss in old age have not yet been reported. DESIGN: A longitudinal study (follow-up time 3.3 years) of the change of bone mineral density (BMD) at the lumbar spine and femoral neck in relation to serum IGF-I. PATIENTS: A population-based sample of 173 elderly men and 107 postmenopausal women without medical conditions or medication known to significantly affect BMD or serum IGF-I levels. MEASUREMENTS: BMD at the lumbar spine and femoral neck at baseline and after a mean follow-up-time of 3.3 years, serum-IGF-I, insulin-like growth factor binding protein 3 (IGFBP-3), sex hormone-binding globulin (SHBG) and biologically available testosterone (BAT). RESULTS: In women, there was a graded negative relationship between quartiles of serum IGF-I and bone loss at the proximal femur (P = 0.04), which persisted after adjustment for potential covariables of bone loss and serum IGF-I. In subgroup analysis the association between serum IGF-I and change in BMD was only apparent in women more than 10 years past menopause (r = + 0,38, P = 0.01). No association between serum IGF-I levels and changes in BMD was observed in men. IGF-I levels were not associated with changes in spinal BMD. CONCLUSIONS: Our data suggest that low circulating levels of IGF-I in elderly women are associated with greater femoral bone loss, and support previous findings of gender differences in the relation between serum IGF-I and BMD in older age.     

Bone metabolism in type 2 diabetes mellitus

Several conditions have been described to cause osteoporosis, including diabetes mellitus. While the relationship between type 1 diabetes and osteopenia is well documented in the literature, data on the presence of this complication in type 2 diabetes have not been well established. We studied a population composed of 66 post-menopausal women with type 2 diabetes and a control population. We examined bone mineral density with the dual-energy X-ray absorptiometry (DXA) technique at the lumbar and femoral levels and, in a subgroup of patients, we also measured the levels of markers of bone remodelling. We found significantly higher levels of bone mineral density at the femoral (but not lumbar) level in the diabetic subjects compared with the control population in all the examined subregions, except Ward's triangle. Moreover, we found higher levels of some markers of bone resorption (urinary calcium and hydroxyproline, telopeptide) in the patients with diabetes, while urinary crosslinks were higher in the controls. On the basis of these results, we suggest that osteoporosis cannot be considered a complication of type 2 diabetes and that, from a metabolic point of view, bone resorption is greater in diabetic patients than in normal subjects, as suggested by the high levels of most of the markers of osteoclastic activity. Received: 16 March 1998 / Accepted in revised form: 24 February 1999     

Bone mineral density and its determinants in diabetes: the Fremantle Diabetes Study

Aims/hypothesis We assessed the effects of type 1 and type 2 diabetes on bone density and metabolism.Materials and methods We analysed bone mineral density (BMD) measured at the hip, spine and forearm using dual energy X-ray absorptiometry in 34 patients with type 1 and 194 patients with type 2 diabetes. Patients were from the community-based Fremantle Diabetes Study, and findings for them were compared with those from normal age- and sex-matched control subjects from the local community. Biochemical and hormonal markers of bone metabolism were measured in a subset of 70 patients.Results After adjusting for age and BMI, there was a lower BMD at total hip (p<0.001) and femoral neck (p=0.012) in type 1 men vs control subjects, but type 1 women and matched controls had similar BMD at each site. There was a higher BMD at total hip (p=0.006), femoral neck (p=0.026) and forearm (p<0.001) in type 2 women vs control subjects, but diabetes status was not associated with BMD in type 2 men after adjustment for age and BMI. Serum oestradiol, BMI, C-terminal telopeptide of collagen type 1 and male sex were consistently and independently associated with BMD at forearm, hip and femoral neck and explained 61, 55 and 50% of the total variance in BMD, respectively, at these sites. Spine BMD was independently associated with BMI and ln(oestradiol).Conclusions/interpretation Men with type 1 diabetes may be at increased risk of osteoporosis, while type 2 women appear to be protected even after adjusting for BMI. Low serum oestradiol concentrations may predispose to diabetes-associated osteoporosis regardless of sex.     

Femoral neck osteopenia in patients with inflammatory bowel disease

Objective: The mechanism of bone loss in patients with inflammatory bowel disease (IBD) is not completely understood. The aim of this study was to assess indices of bone turnover and bone mineral density (BMD) in the lumbar spine and femoral neck in IBD patients.
Methods: Sixty-three patients with Crohn's disease and 41 with ulcerative colitis were studied. Serum bone-specific alkaline phosphatase (B-ALP), osteocalcin, parathyroid hormone (PTH), 25 hydroxyvitamin D, interleukin-6 (IL-6), and urinary N-telopeptide cross linked type 1 collagen (NTX) were determined. BMD of the lumbar spine and femoral neck was determined by dual x-ray absorptiometry in 59 patients.
Results: In the femoral neck 42% of the patients had osteopenia (−2.5 SD < BMD T score < −1 SD) and another 41% had osteoporosis (BMD T score < −2.5). In the spine 34% of the patients had osteopenia and additional 42% had osteoporosis. BMD T scores were lower in the femoral neck compared to the spine. Reduced BMD was unrelated to gender, disease type, lifetime corticosteroid dose, but inversely correlated with disease duration ( r =−0.36 , p < 0.05 ). Serum IL-6 was higher in IBD patients compared to controls. A reduced level of osteocalcin, a marker of bone formation, was present in 7% of patients and an increase in NTX, a marker of bone resorption, in 25% of them. Osteoporotic IBD patients (spine or hip BMD T score < −2.5) had increased serum IL-6, osteocalcin and PTH level compared to nonosteoporotic patients.
Conclusions: There is a high prevalence of reduced BMD at the spine and femoral neck in IBD patients, which is more severe in the hip. Bone turnover in osteoporotic IBD patients is associated with an increase in osteocalcin, PTH and IL-6. IL-6 may play a role in the pathogenesis of bone loss in IBD.     

Effects of raloxifene therapy on circulating osteoprotegerin and RANK ligand levels in post-menopausal osteoporosis

Previous in vitro studies suggest that the anti-resorptive effect of raloxifene might be mediated by changes in several cytokines involved in the bone remodeling process. In this context, the osteoprotegerin (OPG)- receptor activator of NF kappa B ligand (RANKL) system is considered a key component in the osteoclastogenesis regulation. The aim of this study was to determine the effects of raloxifene treatment on serum concentrations of OPG, receptor RANKL and its relationship with biochemical markers of bone turnover and bone mineral density (BMD) in previously untreated women with post-menopausal osteoporosis. We selected 47 post-menopausal women (mean age 63+/-7 yr) with densitometric criteria of osteoporosis. We determined at baseline, 3, 6, and 12 months anthropometric parameters, biochemical markers of bone turnover, serum levels of 25(OH) D, serum levels of OPG and RANKL. BMD (dual-energy x-ray absorptiometry) in lumbar spine (LS) femoral neck and total hip was measured at baseline and 12 months after raloxifene (60 mg/day) treatment. Serum levels of OPG decreased in the 3rd and 6th month of treatment (p<0.001) and returned to basal levels in the 12th month. There was a significant decrease of RANKL levels and OPG/RANKL ratio after 1 yr of raloxifene treatment. In addition, BMD in LS increased significantly (2.5%) in the 12th month of treatment (p=0.031). Finally, the biochemical markers of bone turnover (total alkaline phosphatase, bone alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine cross-linked carboxi-terminal telopeptide of type I collagen) decreased significantly from the 3rd month of treatment. In conclusion, our results support the hypothesis that raloxifene may inhibit osteoclast activity, at least partly modulating the OPG-RANKL system.     

Oestrogen-receptor-alpha gene polymorphism affects response in bone mineral density to oestrogen in post-menopausal women

OBJECTIVE: An oestrogen-receptor-alpha (ERalpha) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ERalpha gene polymorphism is associated with a functional difference, we assessed the response in bone mineral density (BMD) to oestrogen therapy in post-menopausal women in relation to ERalpha gene polymorphism. PATIENTS AND MEASUREMENTS: Subjects consisted of 124 Thai post-menopausal women. Sixty-three of the women were less than 6 years post-menopausal and 61 were more than 10 years post-menopausal with vertebral or femoral osteoporosis as defined by BMD T-score less than - 2.5. Subjects were randomly allocated to receive 0.3 mg (n = 67) or 0.625 mg (n = 57) of conjugated equine oestrogen (CEE). All subjects also took 5 mg medroxyprogesterone acetate. Vertebral and femoral neck BMD were measured at baseline and 1 year after treatment. Data were expressed as mean +/- SEM. Capital P represents the absence of the restriction site while lower-case p indicates the presence of the restriction site. RESULTS: For subjects on 0.625 mg CEE, BMD at L2-4 increased significantly after 1 year in those with pp (n = 20) Pp (n = 29) and PP genotypes (n = 8) (P < 0.001). However, in subjects on 0.3 mg CEE, BMD at L2-4 increased significantly after 1 year in subjects with Pp (n = 34, + 7.6 +/- 1.5%, P < 0.001) and PP genotypes (n = 13, + 6. 9 +/- 1.0%, P < 0.001), but not in those with pp genotype (n = 20, + 2.3 +/- 2.1%, P = NS). After adjusting for age and years since menopause, the change in vertebral BMD was still lower in those without the P allele compared to those with the P allele (P < 0.05). Femoral BMD did not significantly change regardless of dose of CEE and genotype. CONCLUSIONS: We conclude that ERalpha gene polymorphism affects skeletal response to oestrogen in post-menopausal women. The effect of ERalpha gene polymorphism appears to be site-specific and does not relate to biochemical markers of bone turnover. Determination of ERalpha genotype may help identify post-menopausal women who will have more skeletal benefit from oestrogen therapy.     

Effect of hormone replacement therapy on inflammation-sensitive proteins in post-menopausal women with Type 2 diabetes.

AIMS: To test the effect of oral hormone replacement therapy (HRT) on plasma C-reactive protein (CRP), soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1 (ICAM-1) and IL-6 concentrations and leucocyte count in post-menopausal women with Type 2 diabetes. METHODS: Post-menopausal women with Type 2 diabetes (n = 61) were randomized in a double-blind fashion to receive either continuous combined hormone replacement therapy (n = 29) with conjugated equine oestrogen (0.625 mg/day) plus medroxyprogesterone acetate (2.5 mg/day) or placebo (n = 32) for 6 months. Study variables were measured at baseline and at the end of the study. RESULTS: Eight women randomized to hormone replacement therapy and four women assigned to placebo group dropped out of the study. Plasma CRP increased (2.2 mg/l, 95% confidence interval 0.3-4.1 mg/l) significantly (P = 0.02) in women treated with HRT (n = 21) compared with placebo (n = 29) taking baseline CRP, body mass index (BMI) and smoking status into account. Plasma levels of cell adhesion molecules, IL-6 and leucocyte count did not change significantly during the study. CONCLUSIONS: These findings indicate that oral HRT with conjugated equine oestrogen plus medroxyprogesterone acetate increases plasma CRP levels but not necessarily global inflammatory activity in post-menopausal diabetic women. An increase in plasma CRP may potentially increase risk of a cardiovascular event.     

Methotrexate in the treatment of rheumatoid arthritis. II. In vivo effects on bone mineral density

OBJECTIVE: To determine the effect of methotrexate (MTX) on bone mineral density (BMD) in rheumatoid arthritis (RA). METHODS: One hundred and sixteen non-steroid-treated RA subjects (90 women) were studied in a prospective, longitudinal, non-randomized study. Subjects started MTX (n=36) or sulphasalazine (n=23) or continued long-term (>5 yr) treatment with MTX (n=28) or other disease-modifying anti-rheumatic drugs (n=29). BMD was estimated at entry and after 1 yr. Markers of bone turnover were measured at entry and at 1 yr, and additionally at 3 and 6 months in those starting treatment. Bone biopsies were taken before and after MTX treatment in four subjects. The primary outcome was change in BMD Z score and secondary outcomes were changes in bone turnover markers and bone formation by histomorphometry. RESULTS: Univariate analysis of covariance found that MTX at baseline was associated with reduced BMD at the femoral neck. However, femoral neck BMD was also associated with radiological damage score for the hand. Multivariate analysis and discriminant analysis of the subset of post-menopausal women showed that reduced bone density associated with MTX was due to confounders such as disease activity. There was no adverse effect of MTX on bone turnover markers or on measures of bone formation in biopsies. CONCLUSIONS: No adverse effect of low-dose MTX (mean 10 mg/week) on bone formation in RA was found.