The development of bone mineral density and the occurrence of osteoporosis from 15 to 20 years of disease onset in patients with rheumatoid arthritis

OBJECTIVE: To ascertain the occurrence of osteoporosis and the development of central bone mineral density (BMD) in long-term rheumatoid arthritis (RA) METHODS: BMD of the lumbar spine (L2-L4) and the femoral neck were measured by dual-energy X-ray absorptiometry in a cohort of 59 patients (49 women and 10 men) with rheumatoid factor-positive RA followed up for 20 years. BMD measurements were obtained at the 15- and 20-year follow-up visits. RESULTS: At the 15-year check-up the mean age was 61 (SD 13)for men and 54 (SD 11) years for women. Bone densitometry of these patients revealed decreased BMD at both lumbar spine and femoral neck, the mean T-scores being -1.1 [95%CI: -1.6 to -0.6] and -1.3 [95%CI: -1.6 to -1], respectively). Eighteen (31 %) patients thus had osteoporosis (BMD T -score < or = -2.5) and 32 (54%) patients were osteopenic (BMD T-score -1.0 to -2.5). However, when compared with reference values, the decreases in central bone mineral in this patient group were of low degree; the mean Z-score -0.2 [95%CI: -0.7 to 0.2] at the lumbar spine and -0.5 [95%CI: -0.8 to -0.3] at the femoral neck, respectively. After the subsequent five years the mean Z-score increased 0.45 [95%CI: 0.32 to 0.58] at the lumbar spine and the mean T-score decreased -0.20 [95%CI: -0.32 to -0.08] at the femoral neck. ESR, Larsen score, gender and cumulative dose of prednisolone during the 5 year follow-up and HAQ-index were used as explanatory parameters of BMD change between the 15- and 20-year follow-ups. None of these parameters explained the BMD change. CONCLUSION: We conclude that in long-term RA central bone densities seemed to be only moderately decreased after 15 years from eruption of RA. No essential change in central BMD was found after the consecutive 5 years.     

Maintenance infliximab treatment is associated with improved bone mineral density in Crohn's disease

OBJECTIVES: Diminished bone mineral density (BMD) is a recognized complication of Crohn's disease (CD). The mechanisms underlying bone loss are unclear but may include a direct effect of inflammatory cytokines related to disease activity. Because tumor necrosis factor alpha (TNF-alpha) plays a central role in the pathogenesis of CD inflammation, we evaluated the effect on BMD of maintenance treatment with infliximab in patients with CD. METHODS: BMD of the lumbar spine (L2-L4) and proximal left femur (neck and trochanter) were measured at baseline and 1 yr in 46 CD patients treated with infliximab (5 mg/kg) at 6-8 wk intervals for 1 yr. Thirteen patients received concurrent prednisone at a mean dose of 10 mg/day (range: 5-15). RESULTS: At baseline, reduced BMD (T-score 相似文献   

Sickle cell bone disease: response to vitamin D and calcium

Bone disease with osteoporosis and osteomalacia are common in sickle cell disease (SCD). Some patients have vitamin D deficiency and low bone mineral density (BMD). The role of vitamin D and calcium supplementation to restore bone health in SCD has not been well studied. In 14 adults with SCD, we measured 25(OH)D (25-hydroxyvitamin D) and BMD at the femoral neck, lumbar spine, and distal third of the ulna plus radius, along with markers of bone resorption (CTx; C-terminal component of pro-collagen type I) and bone formation (osteocalcin) before and after 12 months of vitamin D(2) and calcium carbonate treatment. Pretreatment, all patients were vitamin D deficient with a mean 25(OH)D level of 11.6 [corrected] +/- 4 [corrected] ng/ml, had low BMD at the lumbar spine (L-spine), 0.87 +/- 0.11 g/cm(2) (mean Z-score of -2.6 3 +/- 0.71 SD and T score of -2.31 +/- 0.75 SD), femoral neck, 0.8 +/- 0.18 g/cm(2) (mean Z-score -1.36 +/- 0.84, T-score -1.14 +/- 0.75), and the distal radius and ulna, 0.6 +/- 0.17 g/cm(2) (mean Z-score -1.18 +/- 0.79, T-score -1.01 +/- 0.74) and had elevated CTx (0.87 +/- 0.5 ng/ml) and osteocalcin levels (12.3 +/- 3.7 ng/mul). After treatment, all patients corrected their 25(OH)D level (34.6 [corrected] +/- 11 [corrected] ng/ml) (P < 0.001) with a 3.6% +/- 3.9% increase in BMD at the L-spine (P = 0.009), 4.6% +/- 8.5% increase at the femoral neck (P = 0.05) and 6.5% +/- 12.6% increase at the distal radius plus ulna (P = 0.09). CTx, osteocalcin, and PTH(i) levels were unchanged. Treatment of adult SCD with vitamin D and calcium can restore 25(OH)D levels to normal and improve BMD, but, markers of bone resorption remained unchanged. Screening for vitamin D deficiency and BMD in SCD patients seems warranted.     

Sex hormone status and osteoporosis in postmenopausal women with rheumatoid arthritis

Sex hormones have important effects on bone, especially in postmenopausal women. These hormones may be of particular significance in patients with rheumatoid arthritis (RA), who have a high frequency of osteoporosis. To examine this, we measured estrogen and androgen concentrations and bone mineral density (BMD) in 49 postmenopausal women with RA and 49 normal postmenopausal women. Compared with the controls, postmenopausal RA patients had significantly reduced levels of estrone (median 18 pmoles/liter versus 49; P < 0.001), dehydroepiandosterone sulfate (DHEAS) (median 0.3 μmoles/liter versus 2.0; P < 0.001), testosterone (median 0.6 nmoles/liter versus 0.95; P < 0.001), and femoral BMD (mean 0.72 gm/cm² versus 0.80; P < 0.002). Prednisolone therapy in 22 patients (mean dosage 8 mg/day) was associated with reductions in estrone and testosterone levels; however, DHEAS and femoral BMD were also decreased in RA patients who were not receiving corticosteroids. Reduced DHEAS levels in postmenopausal women with RA may increase their risk of osteoporosis.     

Calcaneal ultrasonometry in patients with Charcot osteoarthropathy and its relationship with densitometry in the lumbar spine and femoral neck and with markers of bone turnover.

AIMS: To assess calcaneal ultrasonometry in Charcot osteoarthropathy (CO) and to compare it with densitometry measured by dual energy X-ray absorptiometry (DEXA) and with bone remodelling markers. PATIENTS AND METHODS: A group of 16 diabetic patients in the acute stage of CO with a mean age (+/- SD) of 51 +/- 13 years was compared with 26 sex- and age-matched control subjects. Both calcaneal quantitative ultrasound (QUS) parameter stiffness and bone mineral density (BMD) measured in lumbar spine and femoral neck by DEXA were compared. Collagen type I cross-linked C-telopeptides (ICTP) were used for assessment of bone resorption. RESULTS: Patients with acute CO had significantly lower stiffness of the calcaneus in the Charcot and non-Charcot foot (both P < 0.001) and significantly lower femoral neck BMD (P < 0.05) in comparison with the control group. The T-score of stiffness was significantly lower in the Charcot foot compared with the non-Charcot foot (-3.00 +/- 1.39 vs. -2.36 +/- 1.12; P < 0.01) and significantly lower than the mean T-score of BMD in the lumbar spine (-0.57 +/- 1.28; P < 0.001) and femoral neck (-1.58 +/- 1.24; P < 0.05). A significant difference in ICTP (8.49 +/- 4.37 vs. 3.92 +/- 2.55 ng/ml; P < 0.001) between patients with CO and the control group was found, and a significant correlation was demonstrated between ICTP and the T-score of stiffness (r = -0.73; P < 0.01). CONCLUSION: The lower calcaneal QUS parameter stiffness in the Charcot foot in comparison with the control group, with the non-Charcot foot and with BMD in the lumbar spine and femoral neck, and its association with increased bone resorption indicate that calcaneal ultrasonometry may be useful in diagnosing the acute stage of CO and in assessing the risk of foot fracture. Diabet. Med. 18, 495-500 (2001)     

The treatment of osteoporosis in patients with rheumatoid arthritis receiving glucocorticoids: a comparison of alendronate and intranasal salmon calcitonin

Objective The purpose of this study was to assess the effects of alendronate and intranasal salmon calcitonin (sCT) treatments on bone mineral density and bone turnover in postmenopausal osteoporotic women with rheumatoid arthritis (RA) receiving low-dose glucocorticoids.Methods Fifty osteoporotic postmenopausal women with RA, who had been treated with low-dose corticosteroids for at least 6 months, were randomized to receive alendronate 10 mg/day or sCT 200 IU/day for a period of 24 months. All patients received calcium supplementation 1,000 mg and vitamin D 400 IU daily. Bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter was measured annually using dual-energy X-ray absorptiometry. Bone metabolism measurements included urinary deoxypyridinoline (DPD), serum bone alkaline phosphatase (BAP), and serum osteocalcin (OC).Results Over 2 years, the lumbar spine (4.34%, P <0.001), femoral neck (2.52%, P <0.05), and trochanteric (1.29%, P <0.05) BMD in the alendronate group increased significantly. The sCT treatment increased lumbar spine BMD (1.75%, P <0.05), whereas a significant bone loss occurred at the femoral neck at month 24 (–3.76%, P <0.01). A nonsignificant decrease in the trochanteric region was observed in the sCT group (–0.81%). The difference between the groups with respect to the femoral neck and trochanteric BMD was statistically significant ( P <0.001and P <0.05, respectively). The decreases in urinary DPD (–21.87%, P <0.001), serum BAP (–10.60%, P <0.01), and OC (–19.59%, P <0.05) values were statistically significant in the alendronate group, whereas nonsignificant decreases were observed in the sCT group (–5.77%, –1.96%, and –4.31%, respectively). A significant difference was found in the DPD and BAP levels between the two treatment groups in favor of the alendronate group at all time points ( P =0.001 and P <0.05, respectively).Conclusion The results of this study demonstrated that alendronate treatment produced significantly greater increases in the femoral neck BMD and greater decreases in bone turnover than intranasal sCT in RA patients receiving low dose glucocorticoids.     

Disease-modifying antirheumatic drugs and bone mass in rheumatoid arthritis

This article reviews the effects of DMARDs (including biologic agents) on bone metabolism in rheumatoid arthritis (RA). At present there is no evidence that methotrexate, at least at dosages ranging from 5 to 20 mg/week, negatively affects bone mass as measured by DXA (BMD) as documented in both cross-sectional and longitudinal studies. Most studies of cyclosporine (CyA) use reporting a reduction in erosions and joint damage with no adverse effects on bone, did not measure BMD; CyA treatment is associated with a dose-dependent increase of bone turnover as well as a decrease in both animal and human studies; however, its use in RA setting at a dose < or =5 mg/Kg/ day has so far not been associated with clinical relevant adverse effects on bone metabolism. Anti-TNF-alpha agents, infliximab reduced markers of bone turnover in two longitudinal studies. Data on BMD are not available in RA; nevertheless, an increase in BMD has been documented in spondyloarthropathies with infliximab and etanercept. No clinical data concerning BMD are available on leflunomide as well as on the newer biologic agents (adalimumab, rituximab, anakinra).     

Effect of low dose methotrexate on bone density in women with rheumatoid arthritis: results from a multicenter cross-sectional study

OBJECTIVE: To analyze the influence of low dose methotrexate (MTX) on bone using data from a large multicenter, cross-sectional study on bone mineral density (BMD) in women with rheumatoid arthritis (RA). METHODS: We selected 731 female patients with RA divided into 2 groups on the basis of MTX use: never MTX users (n = 485) and MTX users for at least 6 months (n = 246). Demographic, disease, and treatment related variables were collected for each patient. BMD was measured at lumbar spine and proximal femur by dual energy x-ray absorptiometry. Osteoporosis was defined as BMD < -2.5 T-score. RESULTS: The frequency of osteoporosis among never MTX users and MTX users was 29.1% and 28.3% (p = NS) for lumbar spine, and 34.8% and 37.8% (p = NS) for femoral neck, respectively. Mean T-score values at lumbar spine and femoral neck were comparable in the 2 groups, even after adjusting for age, menopausal status, body mass index (BMI), Health Assessment Questionnaire (HAQ) score, and steroid use. The generalized linear model showed that age, menopause, BMI, HAQ score, and steroid use were significant independent predictors of BMD at lumbar or at femoral level, whereas MTX use was not. Logistic procedure showed that only age, HAQ score, and BMI were significantly associated with the risk of osteoporosis. CONCLUSION: We found no negative effect of low dose MTX on BMD in women with RA.     

Decreased axial bone mineral density in perimenopausal women with rheumatoid arthritis--a population based study.

OBJECTIVES--Although periarticular osteoporosis is a well-recognised phenomenon in rheumatoid arthritis (RA), there is considerable controversy over whether RA is associated with more generalised osteoporosis. The aetiology of this bone loss is probably multifactorial, including both life-style risk factors and disease-related determinants. Population-based studies on bone mineral density (BMD) in RA have not previously been conducted, and the purpose of the present cross-sectional population-based study was to determine whether patients with RA are at an increased risk of having osteoporosis. Furthermore, the determinants of BMD in RA patients were investigated. METHODS--BMD at the spine and femoral neck was measured in 143 women with RA. The control group consisted of 1611 women with no disease or taking any drugs known to affect bone metabolism. The study population was a random stratified sample from the Kuopio Osteoporosis Study, which included all perimenopausal women aged 47-56 years residing in Kuopio Province, Eastern Finland in 1989 (n = 14,220). The mean age of the patients at the time of densitometry was 53.7 years. RESULTS--The mean (SD) spinal and femoral neck BMD was significantly lower in patients with RA compared with controls [spine: 1.067 (0.161) v 1.129 (0.157) g/cm2, p < 0.001; femoral neck: 0.851 (0.136) v 0.932 (0.123) g/cm2, p < 0.001]. Analysis of variance showed that at the spine the difference was significant only in patients having corticosteroid treatment, whereas at the femoral neck patients with non-steroid treatment also had significantly lower BMD. When confounding factors were corrected, no significant difference could be found between non-steroid and corticosteroid treated patients with RA, suggesting that the independent effect of corticosteroids on BMD is only minimal. Multiple regression analysis found age, weight and functional grade to be significant predictors of spinal BMD (R2 = 0.403, p < 0.001). In the femoral neck weight, cumulative corticosteroid dose and functional grade were significant predictors of BMD (R2 = 0.410, p < 0.001). CONCLUSIONS--RA is associated with generalised osteoporosis. The physical impairment and body weight are the major determinants of both spinal and femoral bone mass in RA patients. The cumulative corticosteroid dose was also a significant determinant of femoral neck BMD. However, the independent effect of corticosteroids is questionable because the use of corticosteroids may be an indicator of more severe disease.     

BONE MINERAL DENSITY AND THYROID HORMONE THERAPY

The purpose of this study was to evaluate prospectively the evolution of femoral and vertebral bone mineral density (BMD) in hypothyroid subjects treated with replacement doses (mean |Mp SD dose of L-thyroxine = 135 |Mp 32 μg/day) as compared to an untreated group. Vertebral bone density was also measured in other patients who had been treated for at least 2 years with either suppressive (mean dose =154 |Mp 36 μg/day, n= 28) or replacement doses (mean dose = 104 |Mp 52 μg/day, n= 21) according to the thyrotrophin response (TSH) to the thyrotrophin releasing hormone (TRH) administration. In primary hypothyroid patients, a mean decrease of 5.4% (P < 0.01) for vertebral BMD, 7.3% (P <0.01) for trochanter and 7% (P < 0.001) for femoral neck was observed after 1 year of treatment. This loss was unrelated either to age or to menopausal status (ANOVA). A clinical and hormonal state of euthyroidism was reached since the 3rd month of treatment. Fasting urinary calcium/creatinine excretion was increased significantly (P < 0.05) at the 3rd month, and plasma osteocalcin (OC) increased significantly from the 3rd month onwards (P < 0.05) up to the 12th month (P < 0.025). In the cross-sectional study, vertebral BMD was not significantly different from age-matched normal values in patients receiving either substitutive or suppressive doses of LT4. These results suggest that in the case of primary hypothyroidism even appropriate thyroid replacement therapy could lead during the first year of treatment to a significant reduction in vertebral and femoral BMD. However, the fact that an increased fracture rate has not been documented in long-term treated patients, and the results of our cross-sectional study, suggest that this bone mass reduction could be transient and reversible due to new bone formation at the end of the resorptive sequence.     

The deleterious effects of low-dose corticosteroids on bone density in patients with polymyalgia rheumatica

The beneficial effects of corticosteroid therapy in the treatment of rheumatic diseases may be offset by the occurrence of corticosteroid- related osteoporosis. This problem may be overcome by using low-dose corticosteroids; however, the dose of corticosteroids that is both efficacious and skeletal sparing is uncertain. Therefore, the aim of this study was to determine whether low-dose prednisolone treatment results in bone loss and modifies bone turnover. Nineteen patients (12 female, seven male) suffering from polymyalgia rheumatica received 10 mg or less daily, given in reducing dosage, with a range of 2.5-10 mg and an average of 6.0+/-0.2 mg daily (+/-S.E.M.). Prior to the commencement of therapy and at regular intervals during treatment, bone mineral density (BMD) using dual X-ray absorptiometry and circulating biochemical and hormonal determinants of bone turnover were measured. The patients were followed for 14.4+/-1.6 months (range 6-27). They were compared to 19 age-matched controls. Despite a mean exposure dose of 6 mg/day and disease remission, BMD decreased in the patients at the lumbar spine (2.6+/-0.8%, P < 0.01), femoral neck (2.9+/-1.5%, P=0.06), Ward's triangle (5.5+/-2.9%, P=0.06) and the trochanter (4.3+/-1.9%, P < 0.05). Total body bone mass decreased by 50+/-19 g in the first 6 months (P < 0.02), and by 39+/-30 g in the remaining 8 months of follow- up [not significant (NS)]. In the first 6 months, BMD decreased at the lumbar spine (1.7+/-0.9%, P = 0.06). From 6 months to the end of follow- up, BMD decreased by 8.5+/-3.5% at Ward's triangle (P < 0.05) and by 4.8+/-2.5% at the femoral neck (P=0.08). The fall in BMD correlated with the cumulative prednisolone dose at trabecular-rich regions (trunk r=-0.72, P < 0.001; ribs r=-0.53, P < 0.05). Bone resorption, assessed by urinary cross-laps, was 54.7% higher than controls before treatment was started (P < 0.05) and decreased by 23.5+/-7.1% in the first month of treatment when the mean prednisolone dose was 9.1 mg/day, range 5-10 (P < 0.0001). Serum osteocalcin was not suppressed by disease before treatment, decreased by 27.4+/-5.1% during the first month of treatment (P < 0.001), remained suppressed while the daily dose of prednisolone was > 5 mg/day, but returned to baseline below this dose. Serum parathyroid hormone was 19.3% lower in the patients than controls at baseline (NS), and increased by 46.1% (P < 0.05) but was no higher than controls at any time. Muscle strength increased by 20-60% (P < 0.05 to < 0.01). Prophylaxis should be considered in patients receiving > or = 5 mg/day prednisolone daily as bone loss is 2- to 3-fold expected rates. Earlier trabecular bone loss may predispose to spine and rib fracture; later cortical bone loss may predispose to hip fractures. Doses of prednisolone of < 5 mg daily may be skeletal sparing, but may not be efficacious.      

Increased bone mineral density in patients with chronic hypoparathyroidism

Bone mineral density (BMD) has been shown to be increased in postmenopausal females with postthyroidectomy hypoparathyroidism, but it is not known whether similar gains occur in patients with idiopathic hypoparathyroidism. In this study, we measured the BMD of lumbar spine and proximal femur in 14 patients, 8 with idiopathic hypoparathyroidism and 6 with postthyroidectomy hypoparathyroidism, using dual-energy x-ray absorptiometry. Their age ranged from 23-57 yr old, with a mean of 42.5 yr. The results showed that patients with hypoparathyroidism had a higher BMD than the normal age- and sex-matched population. This was particularly evident at the lumbar spine (L2-L4), with positive Z-score of 1.93 +/- 1.03, whereas Z-score at the femoral neck was 1.14 +/- 0.62 SD. Subgroup analysis showed that those with postthyroidectomy hypoparathyroidism had a mean lumbar spine BMD of 1.434 g/cm(2) and femoral neck BMD of 1.026 g/cm(2), compared with a mean BMD of 1.364 g/cm(2) and 1.022 g/cm(2) at spine and hip, respectively, for those with idiopathic hypoparathyroidism. Statistical analysis did not reveal any significant difference in the BMD, T-score, and Z-score of the bone, at these two sites, between the two groups. In conclusion, the state of chronic hypoparathyroidism is associated with increased BMD, especially at the lumbar spine. Those with idiopathic hypoparathyroidism have a similar degree of increase in BMD as those with postthyroidectomy hypoparathyroidism.     

Anti-tumor necrosis factor (TNF) therapy in rheumatoid arthritis: correlation of TNF-alpha serum level with clinical response and benefit from changing dose or frequency of infliximab infusions

OBJECTIVE: To determine the relationship between serum TNF-alpha level and clinical response in rheumatoid arthritis patients treated by infliximab. This could be of value to predict clinical response to infliximab and to determine the optimal dose and interval between dosing of infliximab. RA patients who did not respond adequately to conventional doses (3 mg/kg) of infliximab were studied to see if increasing the dose or frequency of infliximab infusions would be more effective. METHODS: Fifty-five RA patients who fulfilled the American College of Rheumatology criteria and were receiving treatment by anti-TNF-alpha (infliximab 3 mg/kg body weight every 8 weeks) were evaluated by: clinical disease activity using the Richie score index before receiving their scheduled infliximab infusion. Serum level of TNF-alpha, as measured by competitive ELISA assay, was determined immediately before and 9-11 days after receiving infliximab. RA patients who did not respond adequately to treatment with infliximab were given either a larger dose of infliximab or given the infusion at six-week intervals. Their clinical response was then evaluated sixteen months later. RESULTS Patients were divided into 2 groups according to Richie score, active group with score > 10 (score 20.3 +/- 7.7 mean +/- standard deviation, n = 25) and inactive group with scores < or = 10 (score 4.1 +/- 3.2, n = 30). TNF-alpha serum levels pre-infliximab infusion were significantly higher in the active group 76.1 pg/ml than the inactive group 38.0 pg/ml (P < 0.02). Whereas TNF serum level significantly dropped post infliximab in the inactive group (P < 0.05), it did not drop in the active group. The mean level of the post-infusion TNF-alpha serum level was higher (76.6 +/- 93.4 ng/ml) in the-active than the mean level of the post-infusion serum TNF-alpha levels in the inactive group (26.4 ng/ml +/- 7.9) P < 0.01 using the t-test. Increasing the frequency was superior in RA patients' clinical outcome than increasing the dose of infliximab infusions. CONCLUSION: RA patients who responded well to infliximab and had inactive disease at the time of the study have lower levels of serum TNF-alpha which could be further suppressed by the recommended doses of infliximab. RA patients with active disease have higher serum levels of TNF-alpha which could not be suppressed after the recommended doses of infliximab infusion. Changing the frequency of infliximab infusions in the active group was more effective than increasing the dose of infliximab in inducing improved clinical outcome. We suggest that the lack of suppression of TNF-alpha in the active group could be due to inadequate dosing of infliximab or to the presence of a neutralizing antibody directed against infliximab. It remains to be seen if serum TNF-alpha levels could be used as a guide in determining the dose and intervals between dosing of anti-TNF therapy in RA in order to achieve the desired clinical response.     

Bone mineral density in patients with early rheumatoid arthritis treated with corticosteroids

The aim of this study was to evaluate the bone mineral density (BMD) in patients with early rheumatoid arthritis (RA) prior to and 6 months after adding low-dose corticosteroid (CS) treatment. Adult patients (>21 years old) with early RA (symptom duration <1 year) and severe joint pain under maximal dose of nonsteroidal anti-inflammatory drugs (NSAIDS) were started on low-dose prednisone (10 mg/day). Patients were evaluated after 1, 3, and 6 months. Disease activity measures including swollen and tender joint count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were documented, and the dose of prednisone was adjusted according to the level of pain at each visit. BMD of the femoral neck (FN) and lumbar spine (LS) was measured using dual energy X-ray absorptiometry prior to and 6 months after starting CS treatment. Calcium supplements, vitamin D, bisphosphonates, or hormonal therapy that may affect BMD were not permitted during the study. Twenty patients were eligible and 16 completed the study; 75% were female. The mean age was 47.2±12 years and mean duration of symptoms was 7±2 months. The mean BMD at the FN prior to and 6 months after starting CS treatment were 0.8080 g/cm²±0.1145 and 0.8242 g/cm²±0.1122, respectively (p=0.04). The mean BMD at the LS prior to and 6 months after starting CS treatment were 0.9429 g/cm²±0.1406 and 0.9490 g/cm²±0.1277, respectively (p=0.423). There was a significant correlation between the mean change of BMD at the FN and mean change of tender joint count (p=0.01), ESR (p=0.008), and CRP (p=0.006) but not with swollen joint count (p=0.099). However, there was no correlation between the change of BMD at the FN or LS and the change of any of the disease activity measures of every patient. Also, no correlation was seen between the cumulative dose of CS and the change in BMD. BMD increases significantly at the FN in early RA patients 6 months after adding low-dose CS to the treatment.     

Bone mineral density and biological markers of bone repair in patients with adrenal incidentaloma: effect of subclinical hypercortisolism

PURPOSE: Some adrenal incidentalomas produce cortisol in mild excess ('subclinical' Cushing's adenomas) and can potentially induce osteopenia. Their diagnosis is usually based on exclusive tumour uptake on adrenal scintigraphy using 131I-6 beta-methyl-iodo-19-norcholesterol and on inadequate cortisol response to dexamethasone (DXM) suppression tests. The aims of the present study were to evaluate bone mineral density (BMD) and metabolic markers of bone turnover in patients with incidentalomas and to test the effect of mild hypercortisolism on bone parameters. METHODS: Thirty-five patients (13 men, 22 postmenopausal women, 49-76 years) with unilateral incidentaloma were studied. BMD was measured by dual X-ray absorptiometry. Two biochemical markers of bone formation, serum osteocalcin (BGP) and bone alkaline phosphatase (bALP), and two markers of bone resorption, urinary free deoxypyridinoline (D-Pyr) and urinary carboxy-telopeptide of bone type 1 collagen (CTX), were measured by radioimmunoassay. D-Pyr and CTX were corrected for creatinine excretion. RESULTS: Median values of lumbar and femoral T-score were -1.125 and -0.920, respectively, whereas corresponding Z-score values where normal (0.105 and 0.120, respectively). Thirty-nine percent of patients had low serum BGP values and 3% had low bALP values; 16% showed elevated D-Pyr/creatinine values and 23% increased CTX/creatinine values. Patients both with suppression of the contralateral adrenal on scintigraphy and with an inadequate cortisol response to 1 mg DXM (> 50 nmol/L) (n = 14) presented a lower femoral T-score (P < 0.02) and, to a lesser extent, a lower femoral Z-score (P = 0.11) than other patients (n = 21). The proportion of increased values of CTX/creatinine (42% versus 11%, P = 0.08) also tended to be higher in the first than in the second group of patients. These two groups of patients were similar in terms of age, but tumour size was larger (P < 0.04) and plasma ACTH value was lower (P < 0.02) in patients with scintigraphic and endocrine abnormalities. CONCLUSION: Subclinical hypercortisolism defined on the basis of scintigraphic and hormonal criteria seems to contribute to bone loss in patients with adrenal incidentaloma. As other possible side effects of mild hypercortisolism, these findings have to be taken into account in the therapeutic management of these patients.     

Osteoporosis in rheumatoid arthritis: safety of low dose corticosteroids.

Fear of inducing generalised osteoporosis is one reason why corticosteroids are withheld in patients with rheumatoid arthritis (RA). No studies, however, have directly measured bone density in such patients at clinically relevant sites. To assess this risk we measured bone mineral density in the lumbar spine and femoral neck by dual photon absorptiometry in 84 patients with RA, 44 of whom had been treated with low dose prednis(ol)one (mean dose +/- SE 8.0 +/- 0.5 mg/day; mean duration of treatment 89.6 +/- 12.0 months). There were significant reductions in bone mineral density in patients treated with corticosteroids (lumbar 9.6%, p less than 0.001; femoral 12.2%, p less than 0.001) and in those who had not received corticosteroids (lumbar 6.9%, p less than 0.01; femoral 8.9%, p less than 0.001), but the differences between the two groups were not significant. We conclude on the basis of these studies that low dose oral corticosteroids do not increase the risk of generalised osteoporosis in patients with rheumatoid arthritis.     

Risedronate reverses bone loss in postmenopausal women with low bone mass: results from a multinational, double-blind, placebo-controlled trial. BMD-MN Study Group

Our objective was to investigate the efficacy and tolerability of risedronate in postmenopausal women with low bone mass. Women with a mean lumbar spine T-score of -2 or less (n = 543) received 24 months of placebo or risedronate (2.5 or 5 mg/day). All received calcium (1 g/day). The principal outcome measures were bone mineral density (BMD) at the lumbar spine, femoral neck, and femoral trochanter. At 24 months, lumbar spine BMD increased from baseline by 4% with 5 mg risedronate and 1.4% in the 2.5-mg group, compared with no change with placebo. Efficacy was similar in women who were less than 5 yr and more than 5 yr postmenopausal. At 24 months, risedronate (5 mg) had also increased BMD at the femoral neck and trochanter, whereas BMD decreased in the placebo group. BMD increases were seen at all three sites with risedronate (5 mg) after only 6 months of therapy. Risedronate was well tolerated; upper gastrointestinal adverse events were similar to placebo. We conclude that risedronate (5 mg) increases BMD rapidly and effectively and is well tolerated in postmenopausal women with low bone mass, regardless of time since menopause.     

Age-related changes in bone density among healthy Greek males.

Osteoporosis in men is increasingly recognized as a problem in clinical medicine, but it has received much less attention than its counterpart in women. It is termed idiopathic if no known cause of bone disease can be identified clinically or in the laboratory. The true incidence of idiopathic osteoporosis (IO) in males is difficult to estimate because population characteristics and referral patterns differ so widely. The aim of this study was to investigate the incidence of IO in healthy Greek male volunteers by measuring bone mineral density (BMD) at four skeletal sites and examining the relations among age, BMI, and bone status. This type of information has not yet been published. We considered osteoporosis to be present when the BMD was less than or equal to -2.5 SD from the average value for healthy young men. Three hundred and sixty-three normal male volunteers were investigated. The mean age was 51.3+/-8.7 yr, and BMI was 27.5+/-3.7 kg/m2. In all subjects BMD at four skeletal sites - lumbar spine (LS), femoral neck (FN), Ward's triangle (WT), and finally trochanter (T) - was measured using dual-energy X-ray absorptiometry (DEXA). T-score, Z-score and g/cm2 values were estimated. Forty-four subjects (11%) had BMD< or =-2.5 SD (T-score). The mean age and BMI for the men with decreased BMD was 54.8+/-6.4 yr and 26.3+/-3.3 kg/m2, whereas mean age and BMI for those with normal BMD was 51.0+/-8.9 yr and 27.6+/-3.6 kg/m2, respectively. These differences were statistically significant (p<0.001 and p<0.05, respectively). A positive correlation was found between BMI and bone density (g/cm2) at three skeletal sites: LS (r=0.235, p<0.001), WT (r=0.126, p<0.001) and FN (r=0.260, p<0.001). A positive correlation was also found between BMI and T-score at all skeletal sites studied: LS (r=0.276, p<0.001), WT (r=0.133, p<0.05), FN (r=0.233, p<0.001), and T (r=0.305, p<0.001). Finally, a positive correlation was also found between BMI and Z-score: LS (r=0.256, p<0.001), WT (r=0.117, p<0.005), FN (r=0.240, p<0.001), and T (r=0.187, p<0.001). A negative correlation was found between age and bone density (g/cm2) at FN (r=-0.157, p<0.01) and WT (r=-0.183, p<0.001). The same was true between age and T-score at FN only (r=0.137, p<0.05). Furthermore, a similar correlation was found between age and Z-score at LS (r=0.174, p<0.001). When ANOVA one-way analysis was used, a significant difference was found between the different age groups and BMD (g/cm2) at FN, T, and WT (p<0.001 for all sites). For T-score, a significant difference between age groups was found only at FN (p<0.005). Finally, a significant difference in Z-score was found at FN (p<0.001) and LS (p<0.005). When multiple regression analysis was applied, it was found that BMD (g/cm2) at two sites, FN and WT, independently correlated with age and BMI (FN: p<0.001 for both, WT: p<0.01 and p<0.05, respectively). Finally, we found an accelerated trend toward decreased BMD (g/cm2), when the odds ratio was applied. In conclusion, this study demonstrated that 11% of otherwise healthy Greek men had BMD less than or equal to -2.5 SD. A strong association was found between BMD (g/cm2) and age at three skeletal sites when ANOVA one-way analysis was applied. Moreover, BMD was positively correlated with BMI and negatively correlated with age. Currently available data are sparse and much more research is needed to increase our understanding concerning the etiology of this condition as well as illuminating the relationship between bone density and fracture.     

Bone mineral density in patients with irreversible renal failure treated with peritoneal dialysis

Frequency of osteoporosis in patients on dialysis varies in different studies depending of method and measured region of bone mineral density (BMD). The aim of the study was to evaluate the frequency of disturbances of BMD in patients on peritoneal dialysis (PD). We studied 100 patients: 56 on PD and 44 on HD. (49F, 51 M.age mean 54 +/- 29) on dialysis for 6 to 104 months. BMD was measured using dual energy X-ray densitometry (DEXA) in L1-L4 segment of the vertebral column, femoral neck and forearm. The results of the BMD were presented as T-score in the standard deviation of the mean peak bone mass according to WHO criteria. Depending on the region of interest (ROI), osteoporosis was diagnosed in 20% to 70% of women and in 4% to 35% of men. In females the lowest values of BMD were found in forearm (T-score = -3.16 SD), in males it was femoral neck (T-score = -2.87 SD). In these ROI's the lowest values of BMD in both genders were found in patients with the level of iPTH higher than 300 pg/ml. We did not find any significant difference in BMD between patients on PD and HD. Values of bone mineral density were not related to the duration of dialysotherapy and cause of irreversible renal failure. On the results of our study it has been concluded that, enhancement of disturbances of BMD in patients on PD is related to the region of interest, gender of the patient and functional status of parathyroid glands.     

Bone mineral content and density in asymptomatic children with coeliac disease on a gluten-free diet

OBJECTIVES: Osteoporosis is a complication of coeliac disease. A gluten-free diet improves but does not normalize bone mineral density in adult patients. Only limited data are available regarding the influence of the disease and diet on bone mineralization in children. The aim of this study was to evaluate the radial bone mineral content and density in children and adolescents who are asymptomatic on a gluten-free diet. SUBJECTS AND METHODS: The bone mineral content (BMC) and density (BMD) values of the non-dominant radius midshaft in 91 children (53 girls, 38 boys, mean age 11.7 years, mean duration of disease 8.7 years) were determined by single-photon absorptiometry. At the diagnosis and at least three years after commencement of a gluten-free diet, serum calcium, phosphorus, albumin concentrations and alkaline phosphatase activities were measured in all patients, and intact parathormone concentrations in 16 patients. RESULTS: The mean BMC Z-score value in the female adolescent group only was significantly lower than normal (mean Z-score -1.04, P < 0.01). In contrast, the mean BMD Z-score was significantly higher compared to a healthy population both in girls (mean Z-score +1.36, P < 0.001) and in boys (mean Z-score +0.53, P < 0.02), as well as in the total patient group (mean Z-score +1.01, P < 0.001). The radial diameter was significantly smaller than normal in both pre-pubertal and adolescent groups. Serum laboratory parameters of asymptomatic patients were in the normal range. The parathormone mean value was significantly lower after at least three years of gluten-free diet than at diagnosis (mean +/- SD 3.77 +/- 1.07 versus 7.89 +/- 2.54 pmol/l, P < 0.01), but significantly higher compared to controls (2.89 +/- 0.90 pmol/l, P < 0.05). CONCLUSIONS: These data indicate that treated, asymptomatic coeliac children and adolescents have normal or even higher radius mineral density values than controls, but the bone size remains reduced. Although there is no direct evidence of calcium malabsorption in this cohort of coeliac patients, the slightly higher parathormone levels, together with some other factors, particularly delayed puberty, may result in reduced bone size.