Challenges in the diagnosis and management of glucocorticoid‐induced osteoporosis in younger and older adults

Abstract

Objective Glucocorticoids constitute a considerable risk for developing osteoporosis in both younger and older adults. However, currently available bone imaging modalities and fracture‐risk assessment tools do not adequately capture the dramatic changes in bone microarchitecture, heterogeneity of glucocorticoid exposure, the impact of chronic disease and other osteoporosis risk factors on the assessment of osteoporosis in these individuals. Design A narrative review is presented, following a systematic search of the literature from 2000 to 2021. Results Our current appreciation of glucocorticoid‐induced osteoporosis (GIO) is focused on older populations, with limited evidence to guide the investigation, risk assessment and treatment in premenopausal women and men less than 50 years. The impact of the underlying chronic disease on secondary osteoporosis in these younger adults is also poorly understood. Conclusion Through this narrative review, we provide a comprehensive overview of and recommendations for optimising the management of this common cause of secondary osteoporosis younger and older adults.

Glucocorticoid-induced osteoporosis in premenopausal women: management for the rheumatologist

“…A recent review by Herath et al [12 ▪ ] in Clinical Endocrinology suggested that high-risk young patients, including premenopausal women, should be treated with antiresorptive agents (bisphosphonates preferred over denosumab) but that anabolic agents (parathyroid hormone/parathyroid hormone-related protein analogs, romosozumab) should also be considered in some patients. High risk was defined as one of the following: Z score −1.5 or less and exposure to prednisolone greater than 7.5 mg/day for at least 3 months; prior fracture with ongoing exposure to greater than 7.5 mg/day oral glucocorticoid or high cumulative dose of oral glucocorticoid in young adults with Z score less than −2 [12 ▪ ].…”

“…Lifestyle modifications should also be part of any counseling on premenopausal osteoporosis. The avoidance of smoking [43] and excessive alcohol [44] and malnutrition [45] are important [12 ▪ ,41]. Physical activity should be encouraged with the best evidence for resistance exercise and high impact [46–48], which has the dual function of not only preserving bone density but also maintaining strength to prevent falls in the long-term.…”

“…If a woman becomes unexpectedly pregnant, then the bisphosphonate should be stopped immediately. Counseling all premenopausal women contemplating treatment for osteoporosis about the relative lack of high-quality data in this arena is also key [12 ▪ ].…”

Glucocorticoid Effects on Proteoglycans and Glycosaminoglycans

“…GCs are in active use as a companion drug during radiochemotherapy of different brain neoplasms to prevent brain edema, as well as for other malignant tumors. As systemic drugs, GCs affect both the target tumor and the normal tissues, and their long-term use is associated with delayed negative side effects at the molecular, cellular, and clinical level [ 20 , 21 , 22 ], which also fully applies to normal brain tissue during both corticosteroid therapy and GBM treatment.…”

“…However, long-term use of GCs is associated with delayed negative side effects at the molecular, cellular, and clinical level [ 20 , 21 , 22 ], such as undesirable metabolic complications, including the development of type 2 diabetes mellitus [ 23 ] and insulin resistance [ 24 ], accelerated generalized bone loss and increased vertebral and non-vertebral fracture risk [ 25 , 26 ], and predisposition to cardiovascular diseases [ 27 ]. This has become especially important recently due to the active use of GCs during the COVID-19 pandemic and seems to be realized through numerous molecular pathways and mechanisms, including effects of GCs on various cell types and the extracellular matrix (ECM) of any tissue or organ.…”