Osteoporosis is the most common type of metabolic bone disease that is estimated to affect more than 200 million people in the world(1). The prevalence of osteoporosis has risen significantly and will likely increase in the near future due to the aging population.  Glucocorticoid (GC) therapy is used for the treatment of several diseases such as connective tissue disorders, vasculitis, tuberculosis, inflammatory bowel diseases, etc., Glucocorticoid is given in supraphysiological doses in all these diseases. Published literature shows that 1-2% of the adult population is on oral glucocorticoids for various therapeutic indications(2). Long-term Glucocorticoid (LTGC) therapy is associated with an increased risk of vertebral and non-vertebral fractures(3).

Various studies done in the past consistently show deleterious effects of glucocorticoids even with a dose of 2.5 mg of prednisone for more than 3 months duration(4). The risk of fractures in patients who are on long-term glucocorticoids is higher in patients even with a normal bone mineral density measured with Dual energy-Xray-Absorptiometry(DXA)(5). This is because there are many other factors that predispose a person to fractures apart from dual-energy X-ray absorptiometry. The risk of fracture is increased at a higher BMD level in patients with Glucocorticoid-induced osteoporosis (GIO) when compared to post-menopausal osteoporosis(6). Hence, various fracture risk assessment tools like FRAX have been used to identify patients who are at a higher risk of developing fractures(7).

There is an increased risk of fragility fractures in patients who are being initiated on long-term glucocorticoids. Multiple randomized controlled trials have been done in the past with various drugs such as risedronate, zoledronate, denosumab, and teriparatide(8–16). All these drugs have been approved for the treatment of osteoporosis(5,17). Bisphosphonates are the oldest group of drugs that have been proven to be effective in the prevention of glucocorticoid-induced osteoporosis. Multiple RCTs comparing denosumab either with placebo or with bisphosphonates have shown a superior efficacy of denosumab in improving BMD in the lumbar spine(8,9,18,19). A systematic review and meta-analysis have shown that denosumab is superior to bisphosphonates in improving the lumbar spine and distal radius BMD at 12 months(20). Denosumab was superior compared to bisphosphonates in suppressing P1NP and CTX at 12 months(20). Teriparatide is found to be more effective in improving BMD in the Lumbar spine and Femoral neck compared to denosumab(21,22). Teriparatide is superior to denosumab in reducing the risk of vertebral fractures however there is no difference in the risk reduction of non-vertebral fractures(22,23).

The effect of the combination therapy of denosumab and teriparatide has not been studied in the primary prevention of osteoporosis in patients with long-term glucocorticoids. However, RCT done in patients with postmenopausal osteoporosis has shown a superior efficacy of combination therapy with teriparatide and denosumab in increasing the BMD in patients with post-menopausal osteoporosis compared to either of the drugs given alone (24,25).  The data on microarchitectural changes in patients on long-term glucocorticoids and the effect of these drugs on these microarchitectural changes is also scarce in the literature. Moreover, the effect of these drugs in the prevention of GIO has not yet been studied in our population. Most of the studies done in the past in GIO assessed the changes in bone mineral density with various modalities of therapy for the prevention of osteoporosis. Very few studies have studied the changes in bone microarchitecture using High resolution peripheral quantitative computed tomography (HR-pQCT) or bone biopsy.

Hence, the present study will be undertaken to compare the efficacy of the teriparatide and denosumab, alone or both combined together, in patients who are being initiated on long-term glucocorticoid therapy.