Long-Term Use of Denosumab in Giant Cell Tumors and Vertebral Aneurysmal Bone Cysts

Abstract

Introduction: Denosumab is a human monoclonal antibody that binds to the receptor activator of nuclear factor kB (RANKL), it is used in the treatment of Osteoporosis. The Giant Cell Tumor (GCT) and the Aneurysmal Bone Cyst (ABC) use the same RANKL, and for this reason this drug began to be used for its treatment. There is consensus on the use, dose-time and 12-month duration for Denosumab treatment of GCT. Not so for ABC. In unresectable, disabling or recurrent tumors, its use could be for life. The adverse events of the habitual use of the drug are known, but it is not known if these increase with time. The objective of the present work is to identify the possible adverse events of treatment with Denosumab for more than 12 months. Material and Method: Series of cases with a diagnosis of GCT or ABC in spine, treated with Denosumab for more than 12 months. Adverse events are: arthralgia, fatigue, spinal pain, pain in extremities, headache, hypokalaemia, hypocalcemia, osteonecrosis of the jaw, malignant transformation, pathological fractures. Results: Eight patients, 6 TCG and 2 ABC, with a mean age at diagnosis of 25,6 years; presenting a mean treatment of 4.18 years (range 1.7 - 8.7). Of 6 operated patients, 4 had recurrence (2 to 36 months after surgery). One patient had to suspend treatment due to necrosis of the jaw, another hypocalcemia, both returned to treatment when stabilized. Conclusions: A minor adverse event (hypocalcemia) and a major adverse event (jaw bone necrosis) were observed. Level of Evidence IV; Original.

Pérdida de stock óseo no osteoporótico en la columna. Denosumab como herramienta de tratamiento e implicancia

“…29 Se requerirá más investigación para determinar la eficacia y seguridad del denosumab como tratamiento independiente a largo plazo para el TCG, ya que no existe consenso sobre la duración adecuada de la terapia con denosumab en este momento. 29,30 La terapia con denosumab ha tenido efectos en el hueso y en los tejidos circundantes, incluso en un reporte de caso de una paciente de 58 años con TCG en la columna lumbar, los hallazgos histopatológicos de las secciones resecadas después de 10 cursos de denosumab revelaron la presencia de células positivas para RANK alrededor del tejido óseo. 31 El denosumab es una opción terapéutica disponible para las recidivas o los quistes óseos aneurismáticos inoperables o con resección intralesional; se han observado resultados clínicos y radiológicos de calcificación y remisión de la lesión tumoral.…”

“…Se recomienda el suplemento de calcio y vitamina D, además del control radiológico de la mandíbula. 30,32 La osteonecrosis es más frecuente en el maxilar inferior que en el superior y no en otros huesos, esto se debe a su origen embrionario (origen ectomesenquimático), su irrigación vascular y la remodelación ósea, alteradas por distintos fármacos, como el denosumab a altas dosis, pero principalmente en aquellos pacientes que reciben bifosfonatos. 33 Se debe realizar el diagnóstico odontológico que logre diferenciar los procesos infecciosos de la necrosis ósea por radioterapia de cabeza y cuello, principalmente en aquellos pacientes con trauma odontológicos por prácticas o prótesis dentales flojas.…”

Use of Teriparatide in Surgical Planning for Patients With Osteoporosis

“…16,17 Biomechanically, teriparatide increases pedicle screw torque during spinal fusion surgery more efficiently concerning patients without pharmacological treatment (1.28 ± 0.42 Nm) vs control (1.08 ± 0.52). 24 Other pharmacological lines have played an important role in the management of osteoporosis, such as Denosumab, and despite the existence of scientific evidence in the management of postmenopausal osteoporosis 13 and some pathologies such as giant cell tumor in the sacrum, multiple myeloma, and aneurysmal bone cyst; [28][29][30][31] there is still no evidence in the literature of clinical trials, comparative or prospective studies about its usefulness in elective spinal surgery of the osteoporotic patient. 2 Denosumab is the only monoclonal antibody approved by the FDA for the treatment of osteoporosis.…”

Progress on Denosumab Use in Giant Cell Tumor of Bone: Dose and Duration of Therapy

“…In addition, complications, such as atypical femoral fractures may also occur [ 68 ]. Most serious complications occur in patients with unresectable tumors, owing to a long duration of treatment and high cumulative doses [ 100 , 101 ]. However, for PATD, the greatest risk remains LR, with the possibility of malignant transformation, which can lead to serious consequences.…”