Drug Regulators EMEA, Publish Guidance on Clinical Investigations of Medicinal Products Intended for the Treatment of Glucocorticoid-Induced Osteoporosis

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Oral glucocorticoid therapy is widely used for the treatment of a variety of diseases. Approximately 1% of the population is prescribed oral glucocorticoids, and in the elderly this prevalence rises to 2.5% . The association between glucocorticoid therapy and osteoporosis is well documented and exhibits some characteristic features. Bone loss is particularly rapid in the first few months after initiation of therapy, with a slower rate of loss subsequently. Fracture risk also increases rapidly during the early months of therapy and declines after its cessation. Both cortical and cancellous bone are affected, and there is some reversibility of bone loss after cessation or reduction of therapy.
Although the severity of osteoporosis is related to the dose and duration of glucocorticoid therapy, some increase in fracture risk is seen even at daily doses of ≤7.5 mg daily for 3–6 months. Finally, the effect of glucocorticoids on bone fragility is, to some extent, independent of bone mineral density, fractures occurring at a higher bone mineral density (BMD) threshold than in postmenopausal osteoporosis (PMO). Glucocorticoid-induced osteoporosis (GIOP) and PMO share a number of characteristics with respect
to the cellular pathophysiology of bone loss. Increased bone turnover occurs in both conditions, but differs in its time course. In GIOP, an early and transient increase in bone turnover occurs against a background of low bone turnover with reduced bone formation at both tissue and cellular levels. The early increase in bone turnover in GIOP is likely to be a major contributor to bone loss and increased fracture risk within the first few months of initiating therapy and is therefore an important therapeutic target. In PMO, increased bone turnover is consistently observed over time. Both GIOP and PMO are associated with a reduction in bone formation at the cellular level, this effect
being quantitatively greater in GIOP than PMO and associated with a reduction in bone formation at the tissue level. Similar effects on cancellous bone microarchitecture have also been reported in the two conditions, depending on the dose of glucocorticoids used.