Background/Purpose:

Avascular necrosis (AVN) is cellular death of bone components due to interruption of the blood supply resulting in area of ischemic necrosis but may or may not progress to collapse and painful arthritis.  The incidence of AVN in SLE patients is high although the natural history (e.g. prevalence of progression) has not been well characterized.  In 2002, we initiated the APLLE (Avascular Necrosis Prevention with Lipitor in Lupus Erythematosus), trial to assess the effectiveness of statin therapy to prevent the incidence of AVN in any of 12 sites per patient (femoral heads, medial and lateral femoral condyle, tibeal plateau, distal tibia or talar domes) ascertained by comparing baseline to follow up MRI’s at four and nine months.  We could not demonstrate that atorvastatin prevented AVN and the study was terminated in 2008.  We now report on the course of AVN sites that were identified by MRI during the course of the study emphasizing the development of symptomatic (sx) AVN in patients previously asymptomatic.

Methods:

APLLE trial participants were contacted starting 1/2013.  A questionnaire was used to identify sx AVN and a chart review was conducted to collect pertinent information. Sx was defined as interfering with ADL [daily pain and loss of function].  If patient verbalized symptoms, they were invited for an office visit with the nurse practitioner to complete a focused history and physical.

Results:

23 of 42 APLLE participants available for follow-up at mean of 7.35 years; 19F, 4M; 9AA,9H,2C,3A; 18/23(78%) completed 9 month MRI with 5/18(28%) new AVN, 13 sites out of 216.  During intervention trial; 11/23(48%) atorvastatin, 22/23(96%) hydroxychloroquine; During follow up study; 19/23(83%) hydroxychloroquine,3/23(13%) statin, 3/23(13%)bisphosphonate, 0/23 teriparatide.

                                                                                     AVN Site Results: Interventional & Follow up Studies

                                                                                N             # of Patients with AVN         # Total AVN Sites             # Symptomatic           # Asymptomatic 

                          Interventional: Baseline MRI              42                   15/42(36%)                    48/180(27%)                   2/48(4%)                 46/48(96%)

                          Interventional: 9 month MRI               28                   12/28(43%)                     47/144(33%)                  3/47(6%)                  44/47(94%)

                          Follow-up Study                               23                    8/23(35%)                      33/96(34%)                   7/33(21%)                 26/33(79%)

Follow-up study new sx AVN in 3 patients.  1^st patient-2 sites sx delayed 2.5 years requiring bilateral THR, 2^nd patient-2 sites sx delayed 8 years, 3^rdpatient-3 sites, delayed .75, 1 and 4 years.   No sx AVN in the 18 of 23 in follow-up study without AVN in interventional trial.

Conclusion:

Although AVN is a frequent complication of steroid treatment in SLE, MRI studies are sensitive and can overestimate clinically relevant episodes which should be a source of reassurance to patients. Both at baseline of interventional trial (4%) and in follow-up study (21%) AVN infrequently sx.  Results did not demonstrate protective role for statins or medications intended to preserve bone density. Symptomatic progression, often delayed over years (range .75 – 8 years), occurred in 7/33(21%) arguing against need for aggressive intervention in all patients (e.g. bisphosphonates, teriparatide, core decompression).  Future studies will need to identify risk factors for progression to justify randomized controlled trials.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-natural-history-of-asymptomatic-avascular-necrosis-in-a-cohort-of-patients-with-systemic-lupus-erythematosus-treated-with-corticosteroids/