Updates in epidemiology, pathophysiology and management strategies of glucocorticoid-induced osteoporosis

ABSTRACT

Introduction

Endogenous or exogenous (corticosteroid-induced) glucocorticoids (GCs) excess represents, together with diabetes, the most common cause of secondary osteoporosis.

Areas covered

We present a comprehensive overview about the pathophysiology, clinical management and treatment of GCs induced osteoporosis (GIOP). According to PRISMA guidelines, a literature search identifying articles about bone and GCs was done.

Expert opinion

Despite the progress over the years and the increase in therapeutic options, there still are controversial issues about the management of GIOP. These mainly include the failure of BMD or FRAX to completely account for the rapid increase in fracture risk of most GC-treated patients, the understanding about the independent contribution on bone fragility of the underlying disease requiring GCs therapy, and the necessity of clearer information about the anti-fracture efficacy and long term-safety of most therapeutic options. Moreover, there are no specific indications for the management of bone fragility in endogenous hypercortisolism. Notwithstanding the above limitations there is a general consensus to recommend an assessment of fracture risk in all individuals >40 years committed to receive (or continuing) high dose (>7.5 mg of prednisone equivalent) GCs for ≥3 months and in all patients with fragility fracture history.

KEYWORDS:

• Bisphosphonates
• Cushing disease
• denosumab
• fracture
• glucocorticoids
• osteoporosis
• subclinical hypercortisolism
• teriparatide

Article highlights

• Glucocorticoids (GCs) induced osteoporosis (GIOP) is the most frequent cause of secondary osteoporosis worldwide.

• GIOP most frequently arises a consequence of GC therapy (exogenous cortisol excess) but can be also observed in patients with Cushing syndrome or subclinical hypercortisolism (endogenous cortisol excess).

• In both exogenous or endogenous cortisol excess, GIOP 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 loss of bone density.

• To date the clinical management of GIOP is still debated and the recent guidelines differ in their indications for pharmacological intervention. There is however a general agreement on recommending an assessment of fracture risk and a therapy with bone active drugs at least in all individuals committed to receive high dose, GCs for 3 months or longer. Conversely there is no general consensus on the management of fracture risk in patients with endogenous cortisol excess.

• Oral, nitrogen-bisphosphonates (N-BPs) such as alendronate and risedronate actually represent the most prescribed and cost-effective drugs as first line therapy of GIOP.

• In the recent years more potent antiresorptive agents (i.e. zoledronate and denosumab) or compounds with anabolic activity on bone (i.e. teriparatide, abaloparatide and romosozumab) have been approved for the treatment of osteoporosis and are expected to improve the management of GIOP, particularly in patients at highest risk of fractures.

Reviewer disclosures

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

Declaration of interest

L Gennari has received honoraria from Sandoz, Abiogen Pharma and Kyowa Kirin. L Chiodini has received honoraria from Italfarmaco, Sandoz, Eli Lilly and Kyowa Kirin. A Falchetti has received honoraria from AbiogenPharma. D Merlotti has received honoraria from Savio Pharma and UCB Pharma. C Eller-Vainicher has received honoraria from Eli Lilly, Kyowa Kirin and Amgen. 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.

Additional information

Funding

This paper was not funded.