Potential use of bisphosphonates in children with Legg–Calvé–Perthes disease with signs of osteoarthritis. Interim results from a single-center study

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Abstract

BACKGROUND: Legg–Calvé–Perthes disease is a multifactorial disease with a non-inflammatory and avascular mechanism of necrotic lesions. In some cases, children may have more aggressive disease with signs of osteoarthritis. This variant of Legg–Calvé–Perthes disease is characterized by active inflammation of the bone tissue and arthritis, often leading to severe deformity of the femoral head and early coxarthrosis. The problem of treating osteoarthritis in children with Legg–Calvé–Perthe disease is not solved due to the low effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs). Osteoclast inhibition therapy with bisphosphonates in adults with idiopathic aseptic necrosis of the femoral head has been pathogenetically accepted. The use of bisphosphonates in children with Legg–Calvé–Perthe disease and osteoarthritis has not been evaluated.

AIM: The aim of the study was to evaluate the efficacy and safety of bisphosphonates in children with Legg–Calvé–Perthes disease who presented with signs of osteoarthritis.

MATERIALS AND METHODS: The study used data on the treatment of 14 children (mean age 7.5 ± 2.4 years, 71.4% girls) with Legg–Calvé–Perthe disease (at the impression fracture stage) and active hip osteoarthritis. All children had torpid arthritis refractory to NSAID therapy and present for at least 3 months. Treatment included ibandronic acid at 1.0 mg and 1.5 mg per infusion every 3 months in children younger than 7 years old and older than 7 years old, respectively. Five consecutive infusions were performed in the study. Treatment outcomes were assessed at 6, 12, and 18 months based on combined clinical, imaging, and laboratory changes. A modified SCORING OF HIP MRI FOR JIA score was used to assess osteoarthritis activity.

RESULTS: All children showed a decrease in hip pain after the first infusion of ibandronic acid. The inactive phase of osteoarthritis during bisphosphonate treatment was achieved in 78.5% (11) of children after three consecutive infusions and in 21.5% (3) of children after four infusions. Post-infusion reactions were reported in 85.7% (12) of children during the initial phase of bisphosphonate treatment and were transient. Serum erythrocyte sedimentation rate, C-reactive protein, interleukin-6, and tumor necrosis factor-alpha levels were within reference ranges in children with osteoarthritis. Only 28.5% (4) of patients were found to have 25(OH)Vitamin D deficiency at the time of osteoarthritis diagnosis.

CONCLUSIONS: The use of bisphosphonates in children with Legg–Calvé–Perthes disease and osteoarthritis can be considered an innovative pathogenetic treatment option. The data obtained suggest the potential for the use of bisphosphonates in children with Legg–Calvé–Perthes disease. Further follow-up of children in the study group is needed to assess long-term outcomes.

About the authors

Alexey N. Kozhevnikov

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery; Saint Petersburg State Pediatric Medical University

Author for correspondence.
Email: infant_doc@mail.ru
ORCID iD: 0000-0003-0509-6198
SPIN-code: 1230-6803

MD, PhD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg; Saint Petersburg

Dmitry B. Barsukov

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: dbbarsukov@gmail.com
ORCID iD: 0000-0002-9084-5634
SPIN-code: 2454-6548

MD, PhD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Pavel I. Bortulev

H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery

Email: pavel.bortulev@yandex.ru
ORCID iD: 0000-0003-4931-2817
SPIN-code: 9903-6861

MD, PhD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Sergey A. Braylov

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: sergeybraylov@mail.ru
ORCID iD: 0000-0003-2372-9817
SPIN-code: 9369-6073
Russian Federation, Saint Petersburg

References

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Supplementary files

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2. Fig. 4. Magnetic resonance imaging: signs of inactive osteoarthritis in two children with left-sided Legg-Calve-Perthes disease on the background of bisphosphonates, STIR mode

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3. Fig. 1. Magnetic resonance imaging: stage II osteochondropathy of the left femoral head with signs of osteoarthritis. The short-tau inversion recovery mode revealed an extensive destruction zone in the femoral head, reactive trabecular edema in the head and neck, and signs of chronic synovitis

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4. Fig. 2. Magnetic resonance imaging: signs of varying severity of synovitis in the hip joint in children with LCPD. STIR mode images show (a) minimal effusion within the joint capsule, (b, c) moderate synovial fluid accumulation stretching the joint capsule with synovial reaction, and (d) significant synovial fluid accumulation stretching the joint capsule with synovial proliferation

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5. Fig. 3. Magnetic resonance imaging: signs of varying severity of femoral head lesions in children with the Legg–Calvé–Perthes disease. STIR mode images show (a) necrotic lesion and trabecular edema occupying ≤33% of the epiphysis, (b) necrotic lesion and edema occupying 34%–66% of the epiphysis, (c, d) necrotic lesion and edema occupying 67%–100% of the epiphysis

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6. Fig. 5. Changes in pain reduction (visual analog scale, 10-point system) over time

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7. Fig. 6. Pain reduction dynamics (Ritchie articular index for the hip joint) (0, no tenderness during movement; 1 (mild pain), patient reports discomfort; 2 (moderate pain), patient reports discomfort and grimaces; 3 (severe pain), patient withdraws the limb)

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8. Fig. 7. Changes in osteoarthritis activity in children with the Legg–Calvé–Perthes disease during bisphosphonate therapy based on the modified SCORING OF HIP MRI FOR JIA Scale (0–6)

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9. Fig. 8. Serum 25(OH) vitamin D levels in children with the Legg–Calvé–Perthes disease and osteoarthritis before and 6 months after bisphosphonate therapy

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10. Fig. 9. Serum alkaline phosphatase activity in children with the Legg–Calvé–Perthes disease and osteoarthritis before and 6 months after bisphosphonate therapy

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