Osteonecrosis

Definition, Etiology, PathogenesisTop

Osteonecrosis (avascular necrosis of bone) is the end stage of various abnormalities of blood supply to the bone.

Causes:

1) Trauma (in ~50% of patients), particularly fractures of the proximal femur.

2) Nontraumatic causes: Glucocorticoid treatment (particularly involving oral and intra-articular administration; the risk depends on the daily dose and, to a lesser degree, on the duration of treatment and the cumulative dose), alcohol dependence (along with glucocorticoid treatment this accounts for the majority of cases of nontraumatic osteonecrosis), autoimmune diseases (particularly systemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis), myeloproliferative neoplasms, irradiation, gout, sickle cell anemia, thrombophilia, decompression sickness, treatment with denosumab or IV bisphosphonates (osteonecrosis of the jaw, mostly due to long-term use in cancer patients with bony metastases; as an example, about 1 in 1000 patients with multiple myeloma using bisphosphonates will be affected),Evidence 1Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and publication bias. Mhaskar R, Kumar A, Miladinovic B, Djulbegovic B. Bisphosphonates in multiple myeloma: an updated network meta-analysis. Cochrane Database Syst Rev. 2017 Dec 18;12:CD003188. doi: 10.1002/14651858.CD003188.pub4. Review. PMID: 29253322. and other.

3) Idiopathic osteonecrosis: For instance, avascular necrosis of the femoral head in children (Legg-Calvé-Perthes disease).

Osteonecrosis most frequently affects the femoral head and less often involves the femoral condyles, the head of the humerus, or the proximal epiphysis of the tibia, talus, and carpal bones. Involvement may be bilateral, particularly in patients with osteonecrosis of the femoral head. Ischemia of the subchondral part of the trabecular bone leads to its necrosis, deformity of the articular surface, and secondary degenerative and proliferative changes of the joint.

Clinical Features and Natural HistoryTop

Symptoms of osteonecrosis:

1) Localized pain: In patients with osteonecrosis of the femoral head pain is localized in the groin and buttock and referred to the inner thigh and knee. It is aggravated by weight-bearing upon walking but may also be present at rest and at night. Occasionally, the pain may precede radiologic features of necrosis by several weeks or even months. Chronic pain syndrome develops due to degenerative and proliferative changes.

2) Short-lasting morning stiffness (<60 min), which differentiates osteonecrosis from inflammatory conditions, such as rheumatoid arthritis (where the stiffness usually lasts >60 min). The range of motion is not limited until the joint space becomes narrowed and secondary degenerative and proliferative changes develop.

3) Patients with advanced avascular necrosis of the hip or knee have limb shortening and gait abnormalities.

DiagnosisTop

The diagnosis of osteonecrosis is based on imaging studies. An accurate diagnosis is particularly important in the early stages of the disease, when medical treatment is possible in some patients.

In the early stages of osteonecrosis radiography reveals only minor osteopenia; in such cases magnetic resonance imaging (MRI) is the best diagnostic tool. In patients with more advanced disease radiography reveals changes in the trabecular bone, including osteolytic lesions (resorption of necrotic bone tissue), separated necrotic fragments of bone (sequestra), and osteosclerotic remodeling. With the progression of necrotic changes and collapse of the articular surface, patients develop joint space widening. Narrowing of the joint space and deformation of the articular surface appear in late stages of the disease (the “crescent sign” is pathognomonic for subchondral collapse), when secondary degenerative and proliferative changes develop.

Differential Diagnosis

Differential diagnosis mainly includes joint diseases (arthritis, degenerative and proliferative arthropathy), bone disorders (fractures, tumors, infections, metabolic bone diseases), entrapment syndromes (peripheral nerve entrapment), and, in patients with hip and thigh pain, atherosclerosis of the iliac arteries.

TreatmentTop

1. Conservative management includes prevention of the collapse of articular surfaces and of the development of degenerative and proliferative changes (in the case of weight-bearing joints, this is achieved by partial unweighting for 4-8 weeks with the use of crutches or a walking stick) as well as treatment of pain. Depending on the underlying cause, other therapies without clear evidence of efficacy are sometimes tried, including bisphosphonates, statins for glucocorticoid-induced disease, and anticoagulants for thrombophilia-induced disease.

2. Surgical treatment: In patients with early osteonecrosis and preserved joint space, the aim of treatment is stopping the progression of changes. The best results are achieved by removal of necrotic bone fragments to reduce intraosseous pressure and simultaneous grafting of fragments of the trabecular bone with blood vessels and sometimes with joint cartilage (such procedures are not always effective). In advanced disease, after joint space narrowing has developed, joint replacement is performed, especially in the case of involvement of hip or knee joints.

3. Bisphosphonate therapy: The benefit of this treatment is unproven and remains controversial.Evidence 2Weak recommendation (downsides likely outweigh benefits, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and heterogeneity. Yuan HF, Guo CA, Yan ZQ. The use of bisphosphonate in the treatment of osteonecrosis of the femoral head: a meta-analysis of randomized control trials. Osteoporos Int. 2016 Jan;27(1):295-9. doi: 10.1007/s00198-015-3317-5. Epub 2015 Sep 14. PMID: 26370828.

4. Recombinant human parathyroid hormone (1-34) (teriparatide) has been found to improve the rate of resolution of medication-related osteonecrosis of the jaw (MRONJ) in a small clinical trial; however, further studies are needed to confirm this effect.Evidence 3Weak recommendation (downsides likely outweigh benefits, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and heterogeneity. Sim IW, Borromeo GL, Tsao C, et al. Teriparatide Promotes Bone Healing in Medication-Related Osteonecrosis of the Jaw: A Placebo-Controlled, Randomized Trial. J Clin Oncol. 2020 Sep 10;38(26):2971-2980. doi: 10.1200/JCO.19.02192. Epub 2020 Jul 2. PMID: 32614699.