Introduction:
Glucocorticoids, potent immunosuppressants, wield considerable strength in treating diverse ailments. Yet, prolonged usage invites secondary osteoporosis, a condition where bone density diminishes in 30 to 50 percent of cases, rendering bones fragile and susceptible to fractures. The bone's deterioration unfolds in two stages: initially, a swift decline in bone strength within three to six months ensues, orchestrated by glucocorticoids that heighten bone tissue breakdown through osteoclasts. Subsequently, gradual bone loss follows, marked by the reduced formation of new bone cells (osteoblastogenesis) and the demise of existing bone cells (osteoblasts and osteocytes).
What Are Steroids?
Steroids, or corticosteroids, are anti-inflammatory drugs that find utility across a spectrum of conditions spanning gastrointestinal, rheumatological, pulmonary, post-transplantation scenarios, and malignancies. Crafted as synthetic replicas of hormones, they combat swelling and inflammation while curbing immune system activity. Despite their manifold advantages, their relationship with bone health is precarious. Among corticosteroids, glucocorticoids stand out, with their chronic administration often culminating in secondary osteoporosis.
What Is Steroid Induced Osteoporosis?
Steroid-induced osteoporosis, an outcome of prolonged steroid or glucocorticosteroid usage, manifests as secondary osteoporosis, commonly referred to as glucocorticoid-induced osteoporosis (GIOP). This condition alters bone density, resulting in diminished bone mineral density and heightened fracture susceptibility.
The relative fracture risk attributed to glucocorticoid exposure remains steady across various demographics, encompassing sex, age, and underlying medical conditions. Studies suggest a staggering 60 percent rise in the risk of hip fractures and a striking 160 percent elevation in vertebral fractures due to this phenomenon.
What Is the Pathophysiology of Steroid-Induced Osteoporosis?
The pathophysiology of steroid-induced osteoporosis encompasses myriad pathways, each contributing to the intricate cascade of bone deterioration.
1. Effect on Bone Cells
Glucocorticoids profoundly impact bone cells, effortlessly penetrating cell membranes to bind with specialized receptors, specifically glucocorticoid receptors. This intricate binding event translocates into the cell nucleus, the hub of genetic information, whereupon it interfaces with specific DNA regions housing protein synthesis instructions, thereby orchestrating cellular function.
Remarkably, glucocorticoid medications impede the proliferation and maturation of osteoblasts while instigating programmed cell death among their ranks, culminating in diminished bone formation. Moreover, these compounds fortify the longevity of osteoclasts, which are pivotal in bone tissue breakdown.
Simultaneously, they disrupt the vasculature within bone tissue, exacerbating the deleterious effects. By upregulating RANKL (receptor activator of NF-κB ligand) expression, glucocorticoids foster osteoclast differentiation and activation, instigating bone resorption.
2. Effects on Bone Metabolism:
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Glucocorticoids have a dual effect on calcium regulation; they heighten renal excretion while diminishing intestinal absorption. Consequently, this imbalance induces negative calcium equilibrium within the body, fostering secondary hyperparathyroidism. This condition prompts parathyroid hormone (PTH) overproduction by the parathyroid glands, striving to uphold physiological blood calcium levels. Consequently, bone metabolism becomes indirectly influenced by this intricate interplay.
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Additionally, glucocorticoids exert a suppressive effect on the synthesis and release of sex hormones like estrogen and testosterone, which are pivotal in preserving bone integrity. Consequently, diminished levels of these sex hormones precipitate heightened osteoclast activity and bone resorption, culminating in bone depletion.
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Moreover, glucocorticoids impede the transcription process of the IGF-1 (insulin-like growth factor-1) gene, which is crucial for fostering bone formation through the stimulation of type 1 collagen synthesis, which is pivotal in bone tissue composition. This interference indirectly impacts bone metabolism dynamics.
3. Effects on Muscle Mass
Glucocorticoids instigate muscle tissue degradation, precipitating weakness, particularly in the shoulder and hip regions. Furthermore, they prompt the formation of dysfunctional new muscle fibers alongside a reduction in the force exerted by muscle fibers, consequently heightening the vulnerability to falls and fractures. Remarkably, these muscular alterations become discernible as early as one week following the initiation of glucocorticoid therapy.
What Is the Management of Steroid-Induced Osteoporosis?
The approach to managing steroid-induced osteoporosis hinges upon assessing the individual's absolute fracture risk, a determination facilitated by the FRAX (fracture risk assessment tool). This computer-based algorithm computes the 10-year probability of encountering a hip fracture or major osteoporotic fracture, factoring in parameters such as the average daily dosage of glucocorticoid therapy. Utilizing FRAX scores, clinicians discern which patients under glucocorticoid treatment necessitate pharmacologic intervention to avert fractures effectively.
Typically, glucocorticoids ought to be administered at the minimal effective dosage and for the briefest duration feasible. Whenever viable, exploring alternative medications is advisable. For individuals undergoing prolonged corticosteroid therapy, routine evaluations, and counseling sessions are imperative to mitigate fall hazards, enhance nutritional status, cease smoking habits, regulate weight, curtail alcohol intake, and partake in consistent weight-bearing physical activities. Additionally, prompt management is crucial if a patient encounters elevated blood sugar levels resulting from glucocorticoid usage, a condition termed glucocorticoid-induced hyperglycemia.
Different management options include:
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Calcium supplementation is often recommended, particularly in chronic low-dose glucocorticoid use. Research indicates that when combined with vitamin D supplements, such as 50,000 units per week, and a daily calcium intake of 1000 mg (milligram), it effectively mitigates bone mineral density loss.
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Bisphosphonates emerge as the frontline therapy for addressing steroid-induced osteoporosis, owing to their notable efficacy and cost-effectiveness. These medications bind to bone structures, infiltrating osteoclasts and inducing their demise. Notable examples within this class encompass Risedronate, Alendronate, Etidronate, and intravenous Zoledronic acid. However, it is crucial to acknowledge that, while rare, potential complications associated with bisphosphonate use include atypical femoral fractures and osteonecrosis of the jaw.
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Denosumab, an innovative human monoclonal antibody, inhibits RANKL, effectively preventing bone loss. Extensive research suggests that Denosumab exhibits superior efficacy to bisphosphonates in maintaining bone health.
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Teriparatide, a synthetic derivative of human parathyroid hormone, has demonstrated significant efficacy in stimulating bone tissue formation. However, its primary drawback lies in its elevated cost, which can limit its accessibility to some patients.
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Romosozumab, a humanized monoclonal antibody categorized as a sclerostin Inhibitor, emerges as a potent therapeutic option. Sclerostin, a protein renowned for impeding bone formation by inhibiting the Wnt signaling pathway, is effectively countered by Sclerostin inhibitors like Romosozumab. By antagonizing sclerostin, these inhibitors effectively thwart bone loss and foster bone health.
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Medical interventions such as vertebroplasty and kyphoplasty are considered if medications fail to yield the desired response. These procedures involve the injection of bone cement into the fractured region, providing structural support and stability to the affected vertebrae.
Conclusion:
While widely employed for immune system suppression, glucocorticoids harm bone health. Their utilization often triggers swift bone breakdown during the initial months of administration, followed by a gradual pace of bone formation. To mitigate these adverse effects, physicians must exercise prudence by restricting the dosage and duration of glucocorticoid therapy across all patients. Furthermore, patients should receive guidance regarding lifestyle practices conducive to maintaining robust bone integrity. Long-term glucocorticoid users necessitate a thorough assessment of their fracture susceptibility, with consideration given to initiating treatment for those deemed at heightened risk.
