Powerful anti-inflammatories | Used systemically and as joint injections | Major bone and soft-tissue side effects | Osteoporosis and osteonecrosis are the headline harms
TWO WAYS THEY ARE USED
Critical Must-Knows
- Glucocorticoids are anti-inflammatory and immunosuppressive: they bind the cytoplasmic glucocorticoid receptor, alter gene transcription, and suppress inflammatory mediators - powerful relief but with a wide side-effect profile
- Glucocorticoid-induced osteoporosis is the commonest serious systemic harm: bone loss is fastest in the first few months, so fracture risk must be assessed and treated early in anyone on long-term steroids
- Osteonecrosis (avascular necrosis) is the classic orthopaedic complication: corticosteroids are the most common cause of non-traumatic osteonecrosis, the femoral head is the typical site, and it can follow even short high-dose courses
- Intra-articular injection gives real but short-lived pain relief in osteoarthritis, and repeated injection may accelerate cartilage loss - so it is used selectively, not as a long-term solution
- Other effects matter too: impaired wound and fracture healing, raised infection risk, hyperglycaemia, myopathy, and tendon weakening - all relevant when planning surgery in a steroid-treated patient
Clinical Pearls
- "New hip or groin pain in a patient on (or recently on) corticosteroids is osteonecrosis until proven otherwise - early radiographs are often normal, so request an MRI
- "Start bone protection (assess fracture risk, calcium and vitamin D, often a bisphosphonate) early for anyone expected to take 3 months or more of glucocorticoids
- "Patients on long-term steroids cannot mount a normal stress response - give perioperative stress-dose steroid cover to avoid an adrenal crisis
- "Intra-articular steroid relieves pain for weeks, not years - counsel patients that the benefit is temporary
Clinical Imaging
Osteonecrosis of the femoral head - the complication to recognise
Critical Corticosteroid Exam Points
Mechanism
Glucocorticoids cross the cell membrane, bind the cytoplasmic glucocorticoid receptor, and the complex moves to the nucleus to change gene transcription. They switch off inflammatory genes and reduce production of cytokines, prostaglandins, and other mediators. The result is potent anti-inflammatory and immunosuppressive action - and the broad side-effect profile that comes with affecting so many tissues.
Glucocorticoid-Induced Osteoporosis
The commonest serious systemic harm. Steroids suppress bone formation and increase resorption, so bone is lost fastest in the first 3 to 6 months. Assess fracture risk early and treat - do not wait for a fracture.
Osteonecrosis (AVN)
Corticosteroids are the most common cause of non-traumatic osteonecrosis. The femoral head is the classic site, it can follow even short high-dose courses, and it is often bilateral. New hip or groin pain on steroids means MRI.
Around Surgery
Long-term steroids impair wound and fracture healing, raise infection risk, and suppress the adrenal axis - so patients need perioperative stress-dose cover to avoid an adrenal crisis.
Memory aids
BONESCorticosteroid Side Effects
| B | Bone loss (osteoporosis) Fastest in the first few months - assess and treat early |
| O | Osteonecrosis (avascular necrosis) Femoral head, often bilateral, MRI for early disease |
| N | Necrosis of healing - poor wound and fracture repair Plus higher infection risk |
| E | Endocrine and metabolic Hyperglycaemia, weight gain, adrenal suppression |
| S | Soft tissue and muscle Tendon weakening and proximal myopathy |
| B | Bone loss (osteoporosis) Fastest in the first few months - assess and treat early | E | Endocrine and metabolic Hyperglycaemia, weight gain, adrenal suppression |
| O | Osteonecrosis (avascular necrosis) Femoral head, often bilateral, MRI for early disease | S | Soft tissue and muscle Tendon weakening and proximal myopathy |
| N | Necrosis of healing - poor wound and fracture repair Plus higher infection risk |
Hook:Steroids hit the BONES - Bone loss, Osteonecrosis, Necrosis of healing, Endocrine effects, Soft tissue and muscle.
CUSHINGOIDCushingoid Picture of Long-Term Steroids
| C | Cataracts And glaucoma |
| U | Ulcers (peptic) Especially with NSAIDs added |
| S | Skin thinning and striae Easy bruising |
| H | Hypertension and hyperglycaemia Salt and water retention, raised glucose |
| I | Infections Immunosuppression |
| N | Necrosis (avascular) of bone Classic orthopaedic harm |
| G | Glucocorticoid osteoporosis Fracture risk |
| O | Obesity (central) and moon face Fat redistribution |
| I | Immune and adrenal suppression Needs stress-dose cover |
| D | Depression and mood change Plus myopathy |
| C | Cataracts And glaucoma | H | Hypertension and hyperglycaemia Salt and water retention, raised glucose | G | Glucocorticoid osteoporosis Fracture risk | D | Depression and mood change Plus myopathy |
| U | Ulcers (peptic) Especially with NSAIDs added | I | Infections Immunosuppression | O | Obesity (central) and moon face Fat redistribution | ||
| S | Skin thinning and striae Easy bruising | N | Necrosis (avascular) of bone Classic orthopaedic harm | I | Immune and adrenal suppression Needs stress-dose cover |
Hook:The long-term steroid patient looks CUSHINGOID - and the orthopaedic dangers are the bone ones: osteoporosis and osteonecrosis.
CLEANBefore You Inject a Joint
| C | Confirm the diagnosis and indication Pain from inflammation, not infection |
| L | Look for infection Never inject into a possibly septic joint |
| E | Explain temporary benefit Weeks of relief, not a cure |
| A | Aseptic technique Strict sterility to avoid septic arthritis |
| N | Note the limits Avoid repeated frequent injections and mind diabetic glucose |
| C | Confirm the diagnosis and indication Pain from inflammation, not infection | A | Aseptic technique Strict sterility to avoid septic arthritis |
| L | Look for infection Never inject into a possibly septic joint | N | Note the limits Avoid repeated frequent injections and mind diabetic glucose |
| E | Explain temporary benefit Weeks of relief, not a cure |
Hook:Keep it CLEAN before a steroid joint injection - Confirm, Look for infection, Explain, Aseptic, Note the limits.
Overview
Corticosteroids (glucocorticoids) are among the most powerful anti-inflammatory drugs in medicine. In orthopaedics they appear in two very different ways: as systemic therapy for inflammatory and autoimmune disease (where the orthopaedic surgeon usually sees the side effects rather than prescribes the drug), and as local injections into joints, bursae, and tendon sheaths to relieve pain.
For the exam, the key is to understand both the benefit (rapid, strong suppression of inflammation) and the harm, because corticosteroids are heavily examined for their musculoskeletal complications. Three threads recur throughout this topic: how they work, what they do to bone (glucocorticoid-induced osteoporosis and osteonecrosis - the two headline harms), and how to use them safely, both as an injection and around surgery.
Mechanism of Action
Glucocorticoids are lipid-soluble and pass straight through the cell membrane. Inside the cell they bind the glucocorticoid receptor in the cytoplasm. The activated receptor-steroid complex then enters the nucleus and changes which genes are switched on and off.
The two ways they reduce inflammation:
- Switching off inflammatory genes (transrepression): the complex blocks transcription factors such as NF-kB and AP-1, so the cell makes fewer cytokines, fewer adhesion molecules, and less of the enzymes that drive inflammation.
- Switching on anti-inflammatory genes (transactivation): they increase production of proteins such as lipocortin (annexin A1), which inhibits phospholipase A2 and so reduces the release of arachidonic acid - the raw material for prostaglandins and leukotrienes.
The net effect is less inflammation, less immune activity, and less pain. Because the glucocorticoid receptor is present in almost every tissue, the same drug also affects bone, muscle, skin, blood vessels, glucose handling, and the immune system - which is exactly why the side-effect list is so long.
Effects on bone (the orthopaedic core):
How Glucocorticoids Damage Bone
| Process | What the steroid does | Result |
|---|---|---|
| Bone formation | Reduce osteoblast number and activity and increase osteoblast and osteocyte apoptosis | Less new bone is laid down - the dominant effect |
| Bone resorption | Increase osteoclast survival early on (partly via RANKL) | More bone is removed, especially in the first months |
| Calcium balance | Reduce gut calcium absorption and increase urinary calcium loss | A tendency to secondary hyperparathyroidism that further drives bone loss |
| Osteocyte viability | Cause osteocyte apoptosis that is cumulative and not repaired | Loss of the bone's mechanosensors - a key step toward osteonecrosis |
The osteocyte point is high-yield: unlike the gradual thinning of osteoporosis, osteocyte apoptosis is thought to disrupt the bone's ability to sense and repair damage, helping to explain why corticosteroids cause osteonecrosis and not just low bone density.
Agents, Potency and Routes
Common Corticosteroids
| Agent | Relative potency | Typical use in or around orthopaedics | Notes |
|---|---|---|---|
| Hydrocortisone | Low (short-acting) | Intravenous perioperative stress-dose cover; adrenal replacement | Has significant mineralocorticoid (salt-retaining) effect |
| Prednisolone | Intermediate | Oral therapy for inflammatory arthritis and autoimmune disease | The standard oral maintenance steroid |
| Methylprednisolone | Intermediate to high | Intra-articular and soft-tissue injection; intravenous pulses | Common depot injection agent |
| Triamcinolone | High | Intra-articular and soft-tissue injection (depot) | Widely used injectable; long local duration of action |
| Dexamethasone | Very high (long-acting) | Strong anti-inflammatory and anti-emetic uses; negligible salt retention | Most potent of the common agents, long duration |
Relative anti-inflammatory potency runs dexamethasone greater than methylprednisolone greater than prednisolone greater than hydrocortisone. In general, the more potent and longer-acting agents have less mineralocorticoid (salt and water retaining) activity, which is why dexamethasone is favoured when fluid retention must be avoided.
Indications in Orthopaedic Practice
Inflammatory Arthritis
Systemic steroids control flares of rheumatoid arthritis and other inflammatory or autoimmune joint disease; an intra-articular injection can settle a single hot joint.
Osteoarthritis Pain
An intra-articular injection gives short-term pain relief in a flaring osteoarthritic joint - useful as a bridge or for a special event, not as a long-term treatment.
Soft-Tissue and Compressive Conditions
Injection for subacromial bursitis, trigger finger, de Quervain tenosynovitis, and carpal tunnel syndrome, and for enthesopathies such as tennis elbow (where benefit is short-lived and may be no better than other options long term).
Non-Orthopaedic Disease the Surgeon Inherits
Patients are often on long-term steroids for asthma, inflammatory bowel disease, transplantation, or connective-tissue disease - the surgeon must manage the bone, healing, and adrenal consequences.
Clinical Relevance
Corticosteroids run through every part of orthopaedic practice and the exam. In clinic they are the everyday injection for an osteoarthritic knee, a painful shoulder, or a trigger finger - so the indications, technique, and limits of intra-articular steroid are practical knowledge. In basic-science vivas the mechanism of action and the way steroids damage bone are classic questions. In trauma and arthroplasty the recognition of osteonecrosis of the femoral head and the management of a steroid-dependent patient (impaired healing, infection risk, and stress-dose cover) are common scenarios. Knowing when steroids help, what they damage, and how to use them safely is the core that examiners probe.
Evidence: Intra-Articular and Bone Effects
Repeated Intra-Articular Triamcinolone and Knee Cartilage (RCT)
- Two-year double-blind RCT, 140 patients with symptomatic knee osteoarthritis and ultrasound synovitis
- Triamcinolone 40mg every 12 weeks versus saline injection
- Triamcinolone caused significantly greater cartilage volume loss than saline (between-group difference about 0.11mm)
- There was no significant difference in knee pain between the two groups at 2 years
Glucocorticoid-Induced Osteonecrosis - Mechanism and Significance (Review)
- Glucocorticoids are the most common cause of non-traumatic osteonecrosis
- Osteonecrosis develops in roughly 9 to 40 percent of patients on long-term therapy and can follow short high-dose exposure or even intra-articular injection
- The primary lesion is osteocyte apoptosis - a cumulative, unrepairable defect - rather than a single vascular event
- This loss of osteocytes disrupts the bone's mechanosensing and leads to collapse of the femoral head
Preventing and Treating Glucocorticoid-Induced Osteoporosis (ACR Guideline)
- Applies to adults on glucocorticoids for more than 3 months at 2.5mg daily or more
- Strongly recommends early fracture-risk assessment (including bone density and FRAX where appropriate)
- Recommends calcium and vitamin D for all, with an antifracture drug (bisphosphonate, denosumab, or an anabolic agent) for those at medium to very high risk
- Anabolic agents are conditionally preferred as initial therapy for the highest-risk patients
Complications and How to Limit Them
Key Corticosteroid Complications
| Complication | Who and when | What to do |
|---|---|---|
| Glucocorticoid-induced osteoporosis | Long-term systemic use (most loss in first 3 to 6 months) | Assess fracture risk early, give calcium and vitamin D, add a bisphosphonate or other agent by risk |
| Osteonecrosis (avascular necrosis) | High-dose or prolonged use; can follow short courses | New hip or groin pain - MRI even if the radiograph is normal; refer early |
| Impaired healing and infection | Perioperative period in steroid-treated patients | Optimise where possible, watch wounds closely, low threshold to treat infection |
| Adrenal suppression | Long-term use, stopped abruptly or under surgical stress | Do not stop suddenly; give perioperative stress-dose cover |
| Hyperglycaemia | Diabetics and after a steroid injection | Warn diabetics, monitor glucose around systemic dosing and injections |
| Soft-tissue effects | Repeated local injection | Tendon weakening and skin or fat atrophy at the site - avoid injecting into a load-bearing tendon |
Osteonecrosis of the Femoral Head
Corticosteroids are the most common cause of non-traumatic osteonecrosis, and the femoral head is the typical site. The bone dies through a combination of osteocyte apoptosis and impaired blood supply, the dead segment loses its ability to repair, and over time the subchondral bone collapses, leading to pain and secondary osteoarthritis. Early radiographs are often normal, so MRI is the key early investigation, and because the insult is systemic the disease is frequently bilateral.
Clinical Pearl
New hip, groin, or thigh pain in a patient on (or recently on) corticosteroids is osteonecrosis until proven otherwise. A normal radiograph does not exclude it - request an MRI, and image both hips because the disease is often bilateral. Early disease (before collapse) may be amenable to joint-preserving surgery such as core decompression; collapse usually means arthroplasty.
Stopping and the Stress Response
Never stop long-term steroids abruptly - and cover surgical stress
A patient on long-term glucocorticoids has a suppressed adrenal axis and cannot mount the normal cortisol surge that surgery demands. Stopping suddenly, or operating without extra cover, can precipitate an adrenal crisis (hypotension, collapse). Continue the usual steroid, give perioperative stress-dose cover, and wean any long-term course gradually.
Exam Viva Scenarios
Use these scenarios to practise clinical reasoning and management decisions
Mechanism and Bone Effects (~3 min)
"A patient with rheumatoid arthritis is on long-term prednisolone. The examiner asks how corticosteroids work and what they do to bone."
Mechanism: Glucocorticoids are lipid-soluble and bind the cytoplasmic glucocorticoid receptor. The complex enters the nucleus and changes gene transcription - switching off inflammatory genes (reducing cytokines and prostaglandins) and switching on anti-inflammatory proteins such as lipocortin, which inhibits phospholipase A2. The result is potent anti-inflammatory and immunosuppressive action.
Effects on bone: They reduce osteoblast number and activity, increase osteoblast and osteocyte apoptosis, increase resorption early on, and reduce gut calcium absorption while increasing urinary loss. Net effect: rapid bone loss - this is glucocorticoid-induced osteoporosis, with most loss in the first 3 to 6 months.
The osteonecrosis link: Osteocyte apoptosis is cumulative and not repaired, which disrupts the bone's ability to sense and repair damage and helps explain why steroids cause osteonecrosis as well as low bone density.
Practical step: I would assess his fracture risk early and start calcium, vitamin D, and usually a bisphosphonate.
Hip Pain on Steroids (~4 min)
"A 35-year-old man who took high-dose steroids for a flare of inflammatory bowel disease six months ago now has several weeks of right groin pain, worse on weight-bearing. His hip radiograph is reported as normal. How do you proceed?"
Concern: Steroid exposure plus new groin pain is osteonecrosis of the femoral head until proven otherwise, even though the radiograph is normal - early disease is frequently radiograph-negative.
Assessment: Focused history (steroid dose and duration, alcohol, other risk factors) and examination, then MRI of both hips - MRI is the most sensitive early test and the disease is often bilateral, so I would not image only the painful side.
Staging and management: If MRI confirms osteonecrosis, management depends on whether the femoral head has collapsed. Pre-collapse disease can be treated with protected weight-bearing and joint-preserving surgery such as core decompression to try to halt progression. Once the subchondral bone has collapsed, the joint usually deteriorates and total hip arthroplasty becomes the definitive treatment, particularly in a young patient with disabling pain.
Wider care: I would liaise with the team managing his bowel disease to minimise further steroid exposure and address modifiable risk factors.
CORTICOSTEROIDS IN ORTHOPAEDICS
Clinical summary
Mechanism
- •Bind cytoplasmic glucocorticoid receptor, alter gene transcription
- •Switch off inflammatory genes; switch on anti-inflammatory proteins (lipocortin)
- •Potent anti-inflammatory and immunosuppressive
- •Affect almost every tissue - hence the wide side-effect list
Effects on Bone
- •Reduce bone formation, increase early resorption - osteoporosis
- •Most bone loss in the first 3 to 6 months
- •Osteocyte apoptosis drives osteonecrosis
- •Most common cause of non-traumatic osteonecrosis (femoral head, often bilateral)
Intra-Articular Use
- •Short-term pain relief in osteoarthritis and soft-tissue conditions
- •Repeated triamcinolone gave no pain benefit over saline at 2 years and more cartilage loss
- •Strict aseptic technique; never inject a possibly septic joint
- •Warn diabetics about a transient rise in glucose
Red Flags
- •New hip or groin pain on steroids - MRI both hips for osteonecrosis
- •Start bone protection early for courses of 3 months or more
- •Give perioperative stress-dose cover; never stop long-term steroids abruptly
- •Watch for impaired healing and infection after surgery
Guidelines, Registries and Global Practice
- Glucocorticoid-induced osteoporosis guidelines (for example the American College of Rheumatology, and equivalent guidance from NOGG in the UK and other national societies) agree on the core principles: assess fracture risk early, give calcium and vitamin D to all long-term users, and add an antifracture drug (oral bisphosphonate is the usual first choice) for those at moderate or higher risk, with anabolic agents reserved for the highest-risk patients.
- Osteoarthritis guidelines (for example AAOS and NICE) place intra-articular corticosteroid as an option for short-term symptom relief, not as disease-modifying treatment, reflecting trial evidence that the benefit is temporary and that repeated injection may harm cartilage.
- Where guidance differs is mainly the threshold for starting bone-protecting drugs and the place of newer anabolic agents, rather than any disagreement on the underlying harm of long-term steroids.
- Global practice variation largely reflects drug availability and cost (for example the choice between oral and intravenous bisphosphonates or anabolic agents) rather than differences in the principles of safe corticosteroid use.