Bone mineral density in women with systemic lupus erythematosus

The aim of this cross-sectional study was to determine the prevalence of reduced bone mineral density (BMD) in a group of female SLE patients and to identify factors predictive of reduced BMD. Femoral neck (FN) and lumbar spine (LS) dual-energy X-ray absorptiometry results were evaluated in 79 pre- and postmenopausal women with SLE aged (mean, range) 49 (22–73) years). Variables evaluated were disease duration, SLEDAI, current and cumulative corticosteroid dose, Steinbrocker’s functional classification, use of immunosuppressive agents, and history of fracture due to minor trauma. A T-score of ≤1.0 was found in 61.9% at the LS and 48.3% at the FN, and 18 (23.7%) patients belonged to the category of osteoporosis at LS, compared to only three (5.4%) patients at FN. A statistical difference (P= 0.014) was found when comparing LS BMD in pre- and postmenopausal patients. LS BMD had a significant correlation with daily and cumulative steroid dose (P= 0.016 and 0.031, respectively). There was a significant difference in LS BMD between the daily steroid dose group receiving ≤7.5 and those receiving >7.5 mg/day (P= 0.008), and also in FN BMD comparing groups on 0 and >7.5 mg/day (P= 0.022). There was significant difference in LS and FN BMD between patients in Steinbrocker classes I and III (P= 0.016 and 0.005, respectively). No significant correlation was found in either subgroup between BMD and other studied parameters. We concluded that the prevalence of reduced bone mass at LS is pronounced among postmenopausal women with SLE, in those with a high Steinbrocker functional classification and those on a high daily steroid dose. Therefore, these patients should be considered as a high-risk group deserving regular spinal BMD scans and therapy in time to prevent vertebral fractures. Received: 26 March 2000 / Accepted: 18 September 2001     

Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in community dwelling postmenopausal Hungarian women

Hypovitaminosis D can result in low bone mass. The prevalence of hypovitaminosis D has public health implications, especially where data are lacking. Since diet and sunlight are the two souces of vitamin D, the results obtained in one geographical region may not be universally applicable. The aim of this study is to characterize the prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in community dwelling postmenopausal Hungarian women. We determined serum levels of 25-hydroxyvitamin D (25-OH-D), PTH, osteocalcin (OC), degradation products of C-terminal telopeptides of type-I collagen (CTx), dietary calcium intake and BMD at L2–L4 lumbar spine (LS) and femur neck (FN) in 319 randomly selected ambulatory postmenopausal women. The prevalence of hypovitaminosis D (serum 25-OH-D50 nmol/l) was 56.7%. On comparing patients with normal and low 25-OH-D, a significant difference was found in age (61.6±8.5 years versus 67.3±9.9 years; P<0.001), PTH (3.9±1.9 pmol/l versus 4.3±2.7 pmol/l; P<0.05), FN BMD (0.802±0.123 g/cm² versus 0.744±0.125 g/cm²; P<0.001) and dietary calcium intake (714.4±199.4 g/day versus 607.9±233 g/day; P<0.001). Osteoporotic patients had a significantly lower 25-OH-D (37.6±19.8 nmol/l versus 56.4±24 nmol/l; P<0.001) and dietary calcium intake (519.2±244.5 mg/day versus 718.2±164.3 mg/day; P<0.001). After controlling for all other variables, 25-OH-D was found to be significantly associated with age, the average hours of sunshine in the 3 months prior to 25-OH-D level determination and dietary calcium intake (r ²=0.190; P<0.001). For FN BMD, significant independent predictors were age, body mass index, 25-OH-D and dietary calcium intake (r ²=0.435; P<0.001). The prevalence of hypovitaminosis D during spring, summer, autumn and winter was 71%, 46.3%, 49.4% and 56.7%, respectively. There was significant seasonal variation in 25-OH-D, PTH, OC, calcium intake and FN BMD. There is a high prevalence of hypovitaminosis D in healthy postmenopausal Hungarian women, and FN BMD is associated with serum 25-OH-D and dietary calcium intake.     

The effect of 1-year transdermal estrogen replacement therapy on bone mineral density and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus patients: a randomized,double-blind,placebo-controlled trial

We studied the effect of 1-year transdermal estrogen replacement therapy (ERT) on bone mineral density (BMD) and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus (SLE) patients in a randomized, double-blind, placebo-controlled trial. SLE patients were randomly allocated to treatment (estradiol; 50 g transdermal 17-estradiol; n=15) or placebo (n=17) group. Both groups received 5 mg continuous oral medroxyprogesterone acetate, 500 mg calcium and 400 IU vitamin D₃. L₁–L₄ spine (LS), left femur and total hip BMD were measured at baseline and at 6 and 12 months. Serum osteocalcin (OC) and degradation products of C-terminal telopeptides of type-I collagen (CTx) levels were measured at baseline and 3, 6, 9, and 12 months. There was a significant difference in the percentage change of LS BMD at 6 months between the two groups (103.24±3.74% (estradiol group) vs 98.99±3.11% (placebo group); P<0.005). There was a significant decrease within the estradiol group in the CTx levels between baseline and all subsequent visits (P<0.05). There was no significant difference in SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) damage index and corticosteroid dose during the study period. Transdermal estradiol may prevent bone loss in postmenopausal SLE women at the lumbar spine and femur, with no increase in disease activity among postmenopausal SLE women receiving transdermal ERT. The high dropout rate (8/15) leads us to the conclusion that efficacy of HRT in a high-risk group such as SLE women can be attained only in a small number of patients, provided all inclusion/exclusion criteria are strictly adhered to.     

Doppler evaluation of the fetal arterial circulation: reference values of the Resistance Index and Pulsatility Index between the 28th and 41st weeks of gestation]

The authors established reference ranges for the Resistance Index and the Pulsatility Index of the umbilical artery, the fetal descending aorta and the middle cerebral artery in order to facilitate the uniform evaluation of the Doppler ultrasound examination in obstetrics. 164 patients with uncomplicated pregnancies between the 28th and 41st weeks of gestation were recruited for the longitudinal assessment of Doppler Resistance Indices and Pulsatility Indices in the fetal and umbilical arteries. Data were retrospectively analysed in order to establish the weekly mean values and standard deviations. The mean values of the indices in three periods (I.: 28-31, II.: 32-36, III.: 37-41 weeks) were compared. The normal haemodynamic resistance is reflected by the Doppler indices within the weekly mean +/- 2SD range. The results designate decreasing haemodynamic impedance in the umbilical and in the middle cerebral arteries while the resistance to the blood flow in the abdominal aorta is constant throughout the third trimester of gestation. The introduction and the clinical application of the reference values provides appropriate interpretation of the physiologic fetal blood flow patterns which is the prerequisite of the diagnostic accuracy of the Doppler ultrasound in obstetrics.     

Osteoporosis in mixed connective tissue disease

The existence of osteoporosis in 58 postmenopausal women with mixed connective tissue disease (MCTD) was investigated. The mean bone mineral density assessed by dual energy X-ray absorptiometry in the lumbar spine was decreased in 25.8% of the patients, reflecting osteoporosis (T score < –2.5). In the femoral neck there was no significant difference between the BMD of MCTD patients and that of age-matched, healthy postmenopausal women. Low bone mineral density was found among patients on, as well as off, corticosteroids. The extent of bone loss was associated with disease duration, as well as corticosteroid therapy. Serum osteocalcin levels were lower in MCTD patients than in controls. Lower serum oestradiol, testosterone and dehydroepiandrosterone sulphate levels were detected in MCTD patients than in controls. Thus, MCTD may be associated with increased bone loss. Pathogenic factors may include the disease itself, corticosteroid therapy, impaired osteoblast function, and low serum sex hormone levels.     

The effects of pregnancy and lactation on hormonal status and biochemical markers of bone turnover

INTRODUCTION: Biochemical markers of bone turnover are reliable indices for measuring changes in bone formation and bone resorption. Due to limitations in the use of bone densitometry during pregnancy biochemical markers of bone turnover provide an excellent alternative to examine the state of the skeleton during this physiologic state. STUDY DESIGN: We performed a prospective study in 20 women, during their first full term pregnancy until 12 months postpartum, intending to breast feed for 12 (mean, 9.1; range, 7-12) months postpartum. Morning blood and urine samples were obtained for laboratory tests: within 3 months before conception (baseline); between 22 and 24 gestational weeks; after delivery, and 6 and 12 months postpartum. Serum 25-hydroxyvitamin D (25-OH-D), parathyroid hormone (PTH), bone specific alkaline phosphatase, osteocalcin (OC), procollagen I carboxypeptides, calcium, phosphate and creatinine in addition to urine deoxypyridinoline crosslinks and calcium were measured. RESULTS: There was no significant difference in the values of urinary calcium/creatinine and serum calcium, phosphate and 25-OH-D between the different visits during the study. In our patients there was a significant increase in PTH levels at 12 months postpartum as compared to baseline, although the mean values remained in the PTH reference range. All bone turnover markers increased during pregnancy and failed to reach baseline level even 12 months postpartum. CONCLUSION: The high maternal bone turnover may suggest that the calcium needed for infant growth during pregnancy and lactation may be drawn at least in part from the maternal skeleton.     

Pregnancy in women with systemic lupus erythematosus

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder which may be affected by hormonal changes, such as those of pregnancy. Women with SLE have increased adverse pregnancy outcomes. STUDY DESIGN: A retrospective analysis of the gynecologic and immunologic case history of 140 women with SLE and the outcome of 263 pregnancies in 99 women with SLE. RESULTS: In patients diagnosed with SLE, the proportion of pregnancies ending with live birth at term decreased to one-third compared with three quarters in those without a diagnosis of SLE and the incidence of pre-term deliveries and spontaneous abortions increased by 6.8 and 4.7 times, respectively. When SLE was associated with secondary antiphospholipid (APL) syndrome, and lupus anticoagulant (LA) or beta2-glycoprotein antibodies were present, a further increase in the incidence of pregnancy loss was observed. Pregnancy did not cause a flare-up of SLE in all cases, the disease remained stable in about 30% of the patients. Lupus was mild in the majority of the women who carried out their pregnancy to term. We also observed mothers with active SLE who successfully carried out pregnancies to term. CONCLUSION: These findings accord with previous literature and should inform rheumatologists, obstetricians and neonatologists who guide patients in their reproductive decisions.     

The effect of a one-year alendronate therapy on postmenopausal osteoporosis. (Results in Hungary of an international multicenter clinical study)

The FOSIT (Fosamax International Trial) was a placebo-controlled, double blind trial, to determine the effects of daily oral dose of 10 mg alendronate-sodium (Fosamax) or placebo, for one year in postmenopausal osteoporotic women. It was an international, multicenter study; the 153 centers distributed over 34 countries. The number of patients was 1908. Authors report the data of the only Hungarian study site, Debrecen. Twenty women [age (mean +/- SD) 62 +/- 8 years with bone mineral density--BMD--< or = 0.98 g/cm2 at the lumbar spine by LUNAR DPX densitometer] were enrolled into the study and randomly assigned to oral alendronate 10 mg daily or placebo (10 patients in each group). Patients in both groups received 500 mg of calcium. Bone density measurements were performed by dual x-ray absorptiometry (DXA) at months 0, 3, 6, and 12 at the lumbar spine and at the femoral neck. Biochemical indices of bone turnover [bone specific alkaline phosphatase (bAP) and urinary N-telopeptide/creatinine ratio (NTx/crea] were also measured every three months. Percent change of the BMD measurements from baseline at one-year in the alendronate group was +6% and in the placebo group -0.7% on the lumbar spine (p < 0.001). Alendronate treatment increased the bone mineral density in the femoral neck, the trochanter, the Ward's triangle and the total hip by +3.2, +1.6, +3.5, +2.2% respectively, meanwhile the changes in the placebo group were -1.2%; -0.7%; -0.9%; -0.8%, respectively, the difference was not significant. Urinary NTx/crea decreased by 70.6% in the alendronate group and by 9.4% in the placebo group, while bAP decreased by 47.4% in the alendronate group and 15.2% in the placebo group (p < 0.001). In conclusion, after one year of treatment with alendronate induced increase of bone mineral density at the lumbar spine and decreased the bone turnover as compared to the placebo group.     

The Effects of Pregnancy and Lactation on Bone Mineral Density

We performed a prospective study of bone mineral density (BMD) in 38 women during their first full-term pregnancy until 12 months postpartum. BMD measurements at lumbar spine [L2–L4 (LS)] and forearm [distal 33% (RD) and ultradistal (RUD) region of the radius] were made within 3 months before conception, after delivery, and at 6 and 12 months postpartum. In mid-pregnancy the DXA examination was carried out only at the forearm. Patients were grouped according to duration of lactation as group I, II or III (0–1, 1–6, 6–12 months respectively). During pregnancy there was a significant difference between baseline and delivery (p< 0.001) in the LS, RUD and RD BMD values. In group I there was no statistically significant difference in LS BMD between visits following pregnancy. The RUD BMD loss was recovered by 6 months postpartum (PP6). Group II showed continuous bone loss from delivery until PP6 at LS and RUD. In group III the LS BMD loss continued throughout the lactation period. The RUD BMD dropped (4.9%) until PP6 then increased by 3.0% as measured at 12 months postpartum (PP12). There was no significant change in RD BMD in any of three groups during lactation. At LS bone loss between delivery and PP12 correlated well with the duration of lactation (r=−0.727; p<0.001). We suggest that calcium needed for fetal skeletal growth during pregnancy was gained from maternal trabecular and cortical sites and that calcium needed for infant growth during lactation was drawn mainly from the maternal trabecular skeleton in our patients. The effect of pregnancy and lactation on the maternal bone mass was spontaneously compensated after weaning. Received: 13 July 2000 / Accepted: 19 April 2001     

Bone mineral density, biochemical markers of bone turnover, and hormonal status in men with systemic lupus erythematosus

The aim of this study was to evaluate bone mineral density (BMD), biochemical markers of bone turnover, and hormone levels in men with systemic lupus erythematosus (SLE). BMD at L2-L4 lumbar vertebrae (LS), left proximal femur neck, and radius at the ultradistal and mid-33% region was measured by dual-energy X-ray absorptiometry in 23 men with SLE (mean age, disease duration, and cumulative corticosteroid dose were 45.6 years, 11.9 years, and 33.410 g, respectively) and 40 healthy, age- and sex-matched controls. Biochemical markers of bone turnover, parathyroid hormone and 25-hydroxyvitamin D (25-OH-D), testosterone, and dehydroepiandrosterone sulfate (DHEAS) levels were measured. There was no difference in BMD between the SLE and control group. The prevalence of osteoporosis was 17.4% (4 out of 23), found at LS. Biochemical markers of bone turnover were within the reference range. There was a high prevalence of hypovitaminosis D (65.2%), hypotestosteronism (62.5%), and hypodehydroepiandrosterone sulfate (100%). There was no correlation between BMD and duration of disease, corticosteroid doses, SLE Disease Activity Index (SLEDAI), SLE Collaboration Clinics/American College of Rheumatology (SLICC/ARC) damage index, or markers of bone turnover. Bone-specific alkaline phosphatase (BSAP) (r, -0.500; P=0.018) and DHEAS (r, -0.511; P=0.013) correlated with the daily corticosteroid dose. Despite corticosteroid therapy, bone mass in men with SLE was not decreased.