Alendronic acid/efavirenz/emtricitabine/tenofovir disoproxil fumarate

Abstract

Various toxicities and lack of efficacy: case report A 64-year-old man developed bone marrow oedema syndrome, insufficiency fracture and renal insufficiency secondary to tenofovir disoproxil fumarate during treatment with efavirenz/emtricitabine/tenofovir disoproxil fumarate for HIV infection. Additionally, he exhibited lack of efficacy during treatment with alendronic acid for bone marrow oedema syndrome [routes not stated; not all dosages stated]. The man, who had a history of HIV infection, presented to the orthopaedics for a recurrent stress related pain and swelling in both ankle joints and feet of 5 years. He had been receiving efavirenz/emtricitabine/tenofovir disoproxil fumarate [Atripla] for several years with an undetectable viral load. He denied any trauma to the lower extremities, and had no chronic or endocrinological diseases. On presentation, the blood analysis revealed: leucocyte count 4.2 G/l, erythrocytes 4.72 T/L, Hb 13.9 g/dL, haematocrit 43.1%, mean cell Hb 29.4pg, mean corpuscular Hb concentration 32.3 g/dL, mean corpuscular volume 91.3fL, red cell distribution width 14.6%, thrombocytes 220 G/l, vitamin-D 49.6 ng/mL, testosterone 6.32 ng/mL, parathyroid hormone 3.22 pmol/L, sodium 143 mmol/L, calcium 2.39 mmol/L and inorganic phosphate 1.13 mmol/L. The vital parameters were also within normal limits. The T-score in the bone mineral density measurement by dual energy X-ray absorptiometry was found to be 1.5 for the lumbar spine and 1.2 for the right hip. Clinical examination revealed doughy skin of the swollen ankles and distinct pressure pain. He experienced severe ankle pain while walking and his visual analogue scale score was found 8. Conventional X-ray in two planes and MRI of both ankle joints were performed. The conventional images revealed no fractures or detectable degenerative changes, nor local reduction of bone mineral content. Initial MRI showed bone marrow oedema in both feet especially in several tarsalia and metatarsalia. Therapeutically, conservative treatment with physiotherapy, dynamic load reduction, lymphatic drainage, systemic application of NSAIDs as well as a therapeutic trial with alendronic acid 70 mg/week for 6 months were performed. However, the antiresorptive therapy over 6 months showed no effect on pain severity and on bone marrow oedema. The conservative treatment showed slight temporary reduction of the symptoms. Subsequently, he had a recurring pain exacerbation along with bone marrow oedema in both feet. In the further course, oedema occurred in both calcanei and the distal tibial meta and epiphysis. He also developed insufficiency fractures in both calcanei. The progressive bone marrow oedemas were accompanied by normal bone specific blood parameters, but there was a significant increase in creatinine and decrease in glomerular filtration rate, as a result he developed stage 3 renal insufficiency. A diagnosis of bone marrow oedema syndrome, insufficiency fracture and renal insufficiency secondary to tenofovir disoproxil fumarate after efavirenz/emtricitabine/tenofovir disoproxil fumarate administration was made [duration of treatment to reaction onsets not stated]. The man’s antiviral therapy was switched to darunavir [Prezista] and ritanovir [Norvir]. After switching the antiviral therapy, a significant clinical improvement was noted with pain reduction and improving renal function. After 18 months of the therapy adjustment, he remained pain free with no signal alterations in the bone marrow of the left foot and only discrete residual alterations in the right foot on MRI scans. The insufficiency fractures were completely consolidated. The impaired renal function improved to a compensated retention with stage 2, and the viral load remained undetectable.