Glucocorticoids are widely prescribed medications known for their potent anti-inflammatory and immunosuppressive effects. However, prolonged use of glucocorticoids can significantly impact bone health, leading to glucocorticoid-induced osteoporosis (GIOP) in susceptible individuals. Understanding the mechanisms underlying GIOP and implementing effective mitigation strategies are crucial aspects of managing patients on long-term glucocorticoid therapy.

What is the pathophysiology of GIOP?

Glucocorticoids exert their adverse effects on bone through several interconnected pathways that disrupt the delicate balance of bone remodelling. 

The pathophysiology of glucocorticoid-induced osteoporosis (GIOP) involves suppression of osteoblast function, promotion of osteoclast activity, and disruption of calcium metabolism. 

Glucocorticoids inhibit bone formation by suppressing osteoblast differentiation and collagen synthesis while increasing osteoclast-mediated bone resorption. This imbalance leads to reduced bone mineral density and increased fracture risk over time.

How do glucocorticoids cause bone loss?

1. Inhibition of Osteoblast Activity: Glucocorticoids suppress osteoblast function by inhibiting the synthesis of collagen and other proteins crucial for bone matrix formation. This impairment hinders bone formation and repair processes, contributing to decreased BMD.
2. Enhanced Osteoclast Activity: Simultaneously, glucocorticoids stimulate osteoclastogenesis and prolong osteoclast survival, leading to increased bone resorption. This imbalance between bone formation and resorption results in accelerated bone loss and compromised bone strength.
3. Disruption of Calcium Homeostasis: Glucocorticoids interfere with calcium metabolism by reducing intestinal calcium absorption and increasing renal calcium excretion. Chronic exposure to glucocorticoids results in negative calcium balance, further exacerbating bone demineralisation.

What are the risks of glucocorticoids?

1. Duration and Dosage: The risk of developing GIOP is directly related to the cumulative dose and duration of glucocorticoid therapy. Higher doses and longer durations increase the likelihood of bone loss and fracture.
2. Age and Gender: Older adults, especially postmenopausal women, are at higher risk due to age-related bone loss compounded by the bone-depleting effects of glucocorticoids. However, GIOP can affect individuals of any age and gender receiving prolonged glucocorticoid treatment.
3. Underlying Conditions: Patients with chronic inflammatory diseases requiring long-term glucocorticoid therapy, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD), are particularly vulnerable to developing GIOP.

Mitigation strategies for GIOP

1. Calcium and Vitamin D Supplementation: Adequate intake of calcium (1000-1200 mg/day) and vitamin D (800-1000 IU/day) is fundamental in preserving bone health and mitigating the adverse effects of glucocorticoids on calcium metabolism. Calcium supplements should be taken in divided doses to enhance absorption.
2. Bisphosphonates: Oral bisphosphonates, such as alendronate and risedronate, are first-line pharmacological agents for preventing and treating GIOP. These medications inhibit osteoclast-mediated bone resorption, thereby preserving BMD and reducing fracture risk.
3. Teriparatide Therapy: In cases where bisphosphonates are inadequate or contraindicated, teriparatide, a recombinant parathyroid hormone (PTH) analogue, may be considered. Teriparatide stimulates osteoblast activity and bone formation, promoting bone remodelling and improving bone strength. For example, Tricium PTH PEN Injection can be used as a therapeutic option to stimulate bone growth.
4. Lifestyle Modifications: Encouraging patients to engage in regular weight-bearing exercises, such as walking or resistance training, helps maintain bone density and strength. Smoking cessation and moderation of alcohol intake are also crucial in promoting bone health and overall well-being.
5. Regular Monitoring: Monitoring bone health through dual-energy X-ray absorptiometry (DXA) scans is essential for assessing BMD changes over time. Serum calcium and vitamin D levels should also be monitored regularly to ensure optimal bone metabolism and treatment efficacy.

Patient education and follow-up

Educating patients about the potential risks of GIOP and the importance of adherence to prescribed treatments and lifestyle modifications is paramount. Regular follow-up visits allow healthcare providers to evaluate treatment responses, adjust therapies as needed, and address any emerging concerns or complications promptly.

Through comprehensive risk assessment, proactive management strategies, and ongoing patient education, healthcare providers can minimise osteoporosis risk and optimise outcomes for individuals requiring glucocorticoid therapy.