High Prevalence of Osteoporosis and Morphometric Vertebral Fractures in Indian Males Aged 60 Years and Above: Should Age for Screening Be Lowered?

Current guidelines recommend bone mineral density (BMD) measurement in asymptomatic men above age 70 years and vertebral fracture (VF) assessment above 80 years with T-score <-1.0 with risk factors. We studied the prevalence of osteoporosis and morphometric VF in asymptomatic males aged 60 years and above in North India. Free-living community-dwelling men (n = 241, age: mean ± standard deviation 68.0 ± 6.2 years) underwent a detailed history, physical examination, biochemical evaluation, and BMD measurements at 3 sites: lumbar spine, total hip (TH), and femoral neck (FN). Morphometric VF were assessed by instant vertebral assessment using Genant et al's semiquantitative method. We observed osteoporosis, osteopenia, and normal BMD in 19%, 56%, and 25% of subjects, respectively. The decade wise prevalence of osteoporosis in the age groups 60-70 years, 71-80 years, and >80 years was 16.9%, 17%, and 50%, respectively. Mean serum 25OHD levels were 17.2 ± 10.3 ng/mL. Vitamin D deficiency (<20 ng/mL) and secondary hyperparathyroidism (plasma intact parathyroid hormone >65 ng/mL) were present in 68.8% and 45.4%, respectively. VF were present in 29.6% subjects (grade I: 58%, grade II: 32.4%, and grade III: 8.8%). Age and iPTH had significant negative correlation with BMD at FN and TH. Serum 25OHD had no correlation with BMD at any site. The prevalence of VF was positively associated with age (p = 0.018) and negatively associated with BMD at FN (p = 0.002) and TH (p = 0.013). Osteoporosis and VF are common in asymptomatic Indian males aged 60 years and above. Screening for osteoporosis and instant vertebral assessment may be recommended earlier than currently existing guidelines.

Interleukin 27 (IL-27) Alleviates Bone Loss in Estrogen-deficient Conditions by Induction of Early Growth Response-2 Gene.

A growing understanding of the bone remodeling process suggests that inflammation significantly contributes to the pathogenesis of osteoporosis. T cells and various cytokines contribute majorly to the estrogen deficiency-induced bone loss. Recent studies have identified the IL-12 cytokine family as consisting of pro-inflammatory IL-12 and IL-23 and the anti-inflammatory IL-27 and IL-35 cytokines. IL-27 exerts protective effects in autoimmune diseases like experimental autoimmune encephalomyelitis; however, its role in the pathogenesis of osteoporosis remains to be determined. In this report, we study the effect of IL-27 supplementation on ovariectomized estrogen-deficient mice on various immune and skeletal parameters. IL-27 treatment in ovariectomized mice suppressed Th17 cell differentiation by inhibiting transcription factor RORγt. Supplementation of IL-27 activates Egr-2 to induce IL-10 producing Tr1 cells. IL-27 treatment prevented the loss of trabecular micro-architecture and preserved cortical bone parameters. IL-27 also inhibited osteoblast apoptosis through increased Egr-2 expression, which induces anti-apoptotic factors like MCL-1. IL-27 suppressed osteoclastogenesis in an Egr-2-dependent manner that up-regulates Id2, the repressor of the receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis. Additionally, these results were corroborated in female osteoporotic subjects where we found decreased serum IL-27 levels along with reduced Egr-2 expression. Our study forms a strong basis for using humanized IL-27 toward the treatment of post-menopausal osteoporosis.

Utility of Osteoporosis Self-Assessment Tool as a Screening Tool for Predicting Osteoporosis in Indian Men.

The osteoporosis self-assessment tool (OSTA) predicts the risk of osteoporosis in an individual. It is a simple calculation-based tool [wt (kg) - age (yr)/5] and can be used for measuring bone mineral density (BMD). However, OSTA is influenced by ethnicity. We studied the performance of OSTA index as a screening tool for osteoporosis in 257 community-dwelling North Indian men above 50 yr age. Each subject underwent a detailed clinical, dietary, anthropometric, and biochemical assessment and bone density measurement using dual-energy X-ray absorptiometry. As per World Health Organization criteria, osteoporosis, osteopenia, and normal BMD were observed in 17.9%, 58.8%, and 23.3%, respectively. OSTA index ranged between -6.4 and 8.8. OST index ≤2 predicted osteoporosis with a sensitivity of 95.7% and a specificity of 33.6% and an area under the curve for a receiver operating characteristic curve of 0.702. The OSTA index is an effective screening tool for measuring BMD in elderly Indian men and can be used by primary care physicians.

IL-18BP is decreased in osteoporotic women: Prevents Inflammasome mediated IL-18 activation and reduces Th17 differentiation.

IL-18BP is a natural antagonist of pro-inflammatory IL-18 cytokine linked to autoimmune disorders like rheumatoid arthritis. However, its role in post menopausal osteoporosis is still unknown. In this study, we investigated the role of IL-18BP on murine osteoblasts, its effect on osteoblasts-CD4+ T cells and osteoblasts-CD11b+ macrophage co-culture. mIL-18BPd enhances osteoblast differentiation and inhibits the activation of NLRP3 inflammasome and caspase-1 which process IL-18 to its active form. Using estrogen deficient mice, we also determined the effect of mIL-18BP on various immune and skeletal parameters. Ovariectomized mice treated with mIL-18BPd exhibited decrease in Th17/Treg ratio and pro-inflammatory cytokines. mIL-18BPd treatment restored trabecular microarchitecture, preserved cortical bone parameters likely attributed to an increased number of bone lining cells and reduced osteoclastogenesis. Importantly, these results were corroborated in female osteoporotic subjects where decreased serum IL-18BP levels and enhanced serum IL-18 levels were observed. Our study forms a strong basis for using humanized IL-18BP towards the treatment of postmenopausal osteoporosis.