When Medications Borrow from Tomorrow: Glucocorticoids, Bone Health, and the Hidden Cost of Survival

A new review in The Lancet Diabetes & Endocrinology (Hofbauer et al., 2025) takes a deep dive into a problem that doctors have recognized for decades: glucocorticoid-induced osteoporosis. These powerful anti-inflammatory drugs—prednisone, dexamethasone, and their cousins—save lives and control autoimmune disease flares. But they also carry a hidden cost: fragile bones, muscle loss, and disrupted hormones.

The review summarizes how glucocorticoids weaken bone by shutting down bone-building cells (osteoblasts), overstimulating bone-breakdown cells (osteoclasts), and draining calcium reserves. The result is osteoporosis and fractures that can appear within just a few months of treatment. But the story doesn’t stop at the skeleton—it extends to muscle wasting, growth hormone suppression, and loss of sex hormones.

From the Exposure-Related Malnutrition (ERM) perspective, this pattern is no accident. It’s the body’s trade-off strategy under stress:

• Immediate survival is prioritized. Resources are diverted from “expensive” processes like growth, reproduction, and tissue maintenance.

• Fuel is mobilized. Muscle protein is broken down for amino acids, bone is resorbed for calcium and phosphate, and fat is redistributed.

• Anabolic signals are silenced. Growth hormone, IGF-1, and sex steroids are suppressed to conserve energy.

This makes sense for a short-term stress response. But when glucocorticoid exposure is prolonged, what was once adaptive becomes destructive. The very mechanisms that protect us in crisis slowly undermine our long-term resilience.

Mapping Glucocorticoid Effects onto the ERM Staging Model

1. Response (early mobilization)

• ↑ Osteoclast activity → bone resorption releases calcium/phosphate.

• ↑ Muscle proteolysis → amino acids fuel gluconeogenesis.

• ↑ Cortisol suppresses GH/IGF-1 and sex steroid production → saves energy by halting growth and reproduction.

2. Adaptation (sustained exposure)

• Osteoblast suppression and osteocyte apoptosis → impaired bone formation.

• Chronic muscle wasting and weakness.

• Persistent low IGF-1, hypogonadism, and reduced adrenal androgens.

3. Maladaptation (clinical expression)

• Osteoporosis and fragility fractures, often at higher bone density than in postmenopausal osteoporosis.

• Sarcopenia and falls → fractures compounded by frailty.

• Loss of reproductive function, metabolic changes (fat redistribution, insulin resistance).

4. Exhaustion (irreversible compromise)

• Cumulative structural damage (spine, hip, pelvis fractures).

• Frailty syndrome: combined skeletal, muscular, and hormonal decline.

• Persistent energy deficit that the body can no longer reallocate without breakdown.

Why This Matters

Glucocorticoids illustrate the cost of resilience. They show us, vividly, how the body reallocates resources under pressure. The skeleton, muscles, and endocrine system become “accounts” to be drained in service of immediate survival.

The Lancet review reminds clinicians to prevent and treat glucocorticoid-induced osteoporosis with lifestyle strategies, calcium and vitamin D, and protective medications like bisphosphonates or anabolic agents. But the deeper lesson, through the ERM lens, is that chronic stress and chronic exposure to catabolic signals always come with a bill—and we often pay it years later in bone, muscle, and vitality.

📖 Reference:

Hofbauer, L. C., Compston, J. E., Saag, K. G., Rauner, M., & Tsourdi, E. (2025). Glucocorticoid-induced osteoporosis: Novel concepts and clinical implications. The Lancet Diabetes & Endocrinology. https://doi.org/10.1016/S2213-8587(25)00251-7

#Glucocorticoid-induced osteoporosis, #Exposure-Related Malnutrition (ERM), #Bone-muscle-endocrine trade-offs, #Stress adaptation and resilience, #Fracture risk and long-term health