Treatment options for glucocorticoid-induced osteoporosis

ABSTRACT

Introduction

Glucocorticoid (GC) induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. It develops in a dose and time dependent manner, due to a rapid and transient increase in bone resorption, followed by the inhibition of bone formation.

Areas covered

In this review, the authors summarize the pathophysiology of GIOP and give discussion to the clinical management of patients taking GCs, focusing on the currently available drugs that have antiresorptive or anabolic activity on bone.

Expert opinion

Despite the widespread use of GCs and their well-established detrimental skeletal effects, GIOP remains an under-diagnosed and under-treated condition. Indeed, the clinical management of GIOP is still debated, so that the recent guidelines differ in their indications for pharmacological intervention. Either bone mineral density (BMD) or algorithms such as FRAX do not completely account for the remarkable and rapid increase in fracture risk of most GC-treated patients. Moreover, while oral bisphosphonates remain the most used and cost-effective option, the potential increased benefits of more potent antiresorptive agents (e.g. denosumab and zoledronate) or anabolic compounds (e.g. teriparatide) warrant further investigation. Despite the above limitations, the assessment of fracture risk is recommended for all individuals committed to receiving oral GCs for 3 months or longer.

KEYWORDS:

• Bisphosphonates
• denosumab
• fracture
• glucocorticoids
• osteoporosis
• teriparatide

Article highlights

• Glucocorticoid (GC) induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis. However, despite the widespread use of GCs and the advances in the understanding of the detrimental effects of GCs on bone, GIOP still remains an under-diagnosed and under-treated condition.

• GIOP develops in a dose and time dependent manner, and is characterized by a rapid and transient increase in bone resorption, accompanied by a long lasting inhibition of bone formation and of osteocyte activity. As a consequence, fracture risk increases rapidly (within 3 months of GC treatment) and is in part unrelated to BMD.

• Thanks to the recent advances in the understanding of bone biology, the range of approved therapeutic options for the prevention and treatment of GIOP is increased. The evidence of efficacy of most, if not all these drugs is based primarily on BMD changes, since the prevention of fractures was not included among the primary outcome in any of the clinical trials.

• Oral bisphosphonates (alendronate and risedronate) actually represent the most prescribed, cost-effective and recommended medications as first line therapy for GIOP. Other agents such as zoledronate and denosumab demonstrated a more potent antiresorptive effect, leading to higher BMD increases. However, there is still limited information concerning their superiority on the prevention of fracture as well as on the safety-efficacy profile of long-term regimens with these compounds in GIOP.

• Since GIOP is mainly characterized by a defective bone formation, the use of agents acting on osteoblasts and exerting an anabolic effect on bone should be more appropriate. Consistent with this hypothesis, a superiority of teriparatide (the recombinant 34 amino acid peptide of PTH) over alendronate and risedronate has been recently demonstrated in patients under GC treatment.

• Despite other osteoanabolic agents such as abaloparatide (a synthetic PTHrP analogue) and romosozumab (a monoclonal antibody against sclerostin) have been recently approved for the treatment of postmenopausal osteoporosis, their use in GIOP has not yet been established. However, romosozumab, due to its combined anabolic and antiresorptive effect on bone, might become a very compelling treatment option for GIOP in the next future.

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Declaration of interest

L Gennari declares that has received personal fees from Sandoz, outside of the submitted work. I Chiodini further reports personal fees from Italfarmaco, Sandoz, Eli Lilly and Company, Kyowa Hakko Kirin Co., Ltd. all outside the submitted work. Finally, D Merlotti has received personal feels from Italfarmaco and UCB Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.