Harjit Pal Bhattoa

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.

Analysis of risk factors for the development of thrombotic complications in antiphospholipid antibody positive lupus patients

The objective of this study was to characterize risk factors for thrombotic events in lupus patients. A total of 272 lupus patients were followed up for five years during which the presence of aPL antibodies [anticardiolipin (aCL), anti-beta2-glycoprotein I (aβ2GPI) and lupus anticoagulant (LAC)] were determined, and all thrombotic incidents and antithrombotic therapy-related data were collected. At baseline, three groups were constituted, an aPL–group with 107 aPL negative patients, an aPL+ group with 81 aPL positive patients without clinical thrombosis and a secondary antiphospholipid syndrome (APS) group with 84 aPL+ patients who met the Sapporo criteria. LAC was more common in the APS than the aPL+ group (32.1% versus 9.9%, P < 0.001). The prevalence of clinical thrombotic events was significantly higher when all three types of aPL were present compared to only aCL positive cases. During follow up, aPL appeared in 7.5% of the aPL - group, and 2.8% of this group had thrombotic complications. In the aPL + group, thrombotic events reoccurred in 1.9% of those receiving antithrombotic prophylaxis and 6.9% of those without primary prophylaxis. Despite anticoagulant therapy, thrombotic events reoccurred in 8.3% of the APS group. These findings indicate that LAC, constant and cumulative presence of aPL and previous thrombosis are positive predictors for the development of thrombotic complication in lupus patients.

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.

Vitamin D Status in Central Europe

Little published information is available regarding epidemiological data on vitamin D status in the large geographical region of Central Europe (CE). We searched the journal literature with regard to 25(OH)D concentrations among community-dwelling or healthy people living in CE. 25(OH)D concentrations varied by age, season, study sample size, and methodological approach [i.e., 25(OH)D assay used]. Concentrations of 25(OH)D in CE appeared lower than 30 ng/mL, and the magnitude of hypovitaminosis D was similar to that reported in Western Europe. While most of the studies reviewed were cross-sectional studies, a longitudinal study was also included to obtain information on seasonal variability. The longitudinal study reported wintertime 25(OH)D values close to 21–23 ng/mL for all studied age groups, with a significant increase of 25(OH)D in August reaching 42 ng/mL for those aged 0–9 years, but only 21 ng/mL for the elderly aged 80–89 years. The decrease in 25(OH)D with respect to age was attributed to decreased time spent in the sun and decreased vitamin D production efficiency. Based on the literature review on vitamin D status in the CE populations, it can be concluded that 25(OH)vitamin D levels are on average below the 30 ng/mL level.

Primary antiphospholipid syndrome as the forerunner of systemic lupus erythematosus

The objective of this study was to analyse whether primary antiphospholipid syndrome (PAPS) may precede and modify the characteristics of systemic lupus erythematosus (SLE). Out of the total 362 SLE patients in our service, 223 patients had antiphospholipid antibodies (aPL), of whom 110 met the criteria of antiphospholipid syndrome. In 26 cases (7.2%) PAPS appeared 5.5 years before the onset of lupus (PAPS+SLE Group). Their clinical findings were compared to lupus patients without (SLE only Group, n = 26) and with secondary APS (SLE+SAPS Group, n = 26). The prevalence of deep venous thrombosis, stroke/TIA, recurrent fetal loss, coronary heart disease and myocardial infarction was significantly higher in PAPS+SLE Group as compared to SLE only Group. The difference in prevalence of fetal loss (P = 0.014) between PAPS+SLE and SLE+SAPS Groups was also recorded. On comparison to PAPS+SLE Group, patients without APS (SLE only Group) were younger at onset of lupus, with more frequent flares and a higher prevalence of WHO type III/IV nephritis (P = 0.007), requiring higher doses of cyclophosphamide and corticosteroids. Lupus started in the form of PAPS in 7.2% of our SLE patients, who presented with more thrombotic and less inflammatory complications than in SLE patients without a prior or with a following secondary APS. Considering the long latency between the two diseases, PAPS may be a forerunner of lupus, but it may also coexist with SLE as an independent autoimmune disorder. Lupus (2007) 16 , 324—328.

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.

Vitamin D supplementation guidelines

Research carried out during the past two-decades extended the understanding of actions of vitamin D, from regulating calcium and phosphate absorption and bone metabolism to many pleiotropic actions in organs and tissues in the body. Most observational and ecological studies report association of higher serum 25-hydroxyvitamin D [25(OH)D] concentrations with improved outcomes for several chronic, communicable and non-communicable diseases. Consequently, numerous agencies and scientific organizations have developed recommendations for vitamin D supplementation and guidance on optimal serum 25(OH)D concentrations. The bone-centric guidelines recommend a target 25(OH)D concentration of 20ng/mL (50nmol/L), and age-dependent daily vitamin D doses of 400-800IU. The guidelines focused on pleiotropic effects of vitamin D recommend a target 25(OH)D concentration of 30ng/mL (75nmol/L), and age-, body weight-, disease-status, and ethnicity dependent vitamin D doses ranging between 400 and 2000IU/day. The wise and balanced choice of the recommendations to follow depends on ones individual health outcome concerns, age, body weight, latitude of residence, dietary and cultural habits, making the regional or nationwide guidelines more applicable in clinical practice. While natural sources of vitamin D can raise 25(OH)D concentrations, relative to dietary preferences and latitude of residence, in the context of general population, these sources are regarded ineffective to maintain the year-round 25(OH)D concentrations in the range of 30-50ng/mL (75-125nmol/L). Vitamin D self-administration related adverse effects, such as hypercalcemia and hypercalciuria are rare, and usually result from taking extremely high doses of vitamin D for a prolonged time.

Occurrence of malignancies in Hungarian patients with systemic lupus erythematosus: results from a single center.

abstract:  As a result of increasing life expectancy of lupus patients, malignant disorders have become major determinants of morbidity and mortality. The objectives of this study were to analyze cancer‐associated morbidity and mortality, the type of malignancies in Hungarian lupus patients, and to analyze association with immune‐suppressive therapy, disease duration, and age of the patients. Data from 860 systemic lupus erythematosus (SLE) patients were retrospectively analyzed in a study period between 1970 and 2004. Results were compared to data from age‐ and sex‐matched population obtained from the Health for All database, and also to literature data. A total of 37 patients presented with cancer, reflecting 4.3% cancer‐associated morbidity. Patients were 47 (20–73) years old at the onset of malignancy, which appeared 13 (1–45) years later than SLE. Cancer prevalence was the highest in the first 5–10 years of lupus. Breast cancer was the most common malignancy (n= 11) followed by gastrointestinal tumors (n= 9), cervix cancer and hematologic malignancies (n= 5 for both), bronchial cancer (n= 4), bladder, skin, and ovarian cancer (n= 1 for each). Standardized incidence ratio was the highest for non‐Hodgkin lymphoma (standardized incidence ratio [SIR] 3.5, 95%CI 0.4–12.5) and cervix cancer (SIR 1.7, 95%CI 0.6–4.1). Although 76% of patients with cancer received immune‐suppressive therapy besides corticosteroids, no direct correlation could be confirmed between therapy and malignancy. Out of the 164 patients that expired during the study period, 18 were cancer‐related. As such the cancer‐associated mortality was 11% (18/164). This peaked during the last 4 years of the study period (8/24, 33%). Lupus patients are at high risk for particular types of malignant disorders, highlighting the importance of screening measures and focused patient examination.

Bone mineral density in women with systemic lupus erythematosus

Abstract: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.

Vitamin D and cardiovascular disease: From atherosclerosis to myocardial infarction and stroke

There continues to be interest in understanding the role of vitamin D in the pathogenesis, epidemiology and prevention of cardiovascular disease (CVD). In fact vitamin D deficiency has been associated to an increased risk of developing CVD given to the relationship between low vitamin D levels and obesity, diabetes mellitus, dyslipidaemia, endothelial dysfunction and hypertension. However, although vitamin D has been identified as a potentially important marker of CVD, the mechanisms through which vitamin D deficiency leads from endothelial dysfunction to myocardial infarction and stroke are not fully understood. Thus, the goal of this review is to provide an updated review of the literature on the basic science of how vitamin D may affect the cardiovascular system and in particular to analyze the role that vitamin D may have in the whole dynamic process from the initiation of endothelial dysfunction to the development of myocardial infarction and stroke.