Zoledronic Acid Compared to Percutaneous Treatment in Osteoid Osteoma
Zoledronic Acid Compared to Percutaneous Treatment in Osteoid Osteoma
Osteoid osteoma (OO) is a benign osteogenic tumor occurring in children and young adults,
 responsible for intense bone pain, which has a tendency to spontaneously heal with
 mineralization of the nidus, but extremely slowly. This healing may be accelerated in
 patients taking NSAIDs regularly during a few years. The long delay for healing and intense
 pain, explain why patients are quickly directed to surgeons or specialized radiology
 departments for tumor ablation. But percutaneous treatment or surgical excision destruction
 can expose the patient to a substantial risk in terms of neurologic or joint damages,
 depending on the location. Bisphosphonates treatment may be an effective alternative to
 percutaneous treatment by accelerating the natural history of OO.
Osteoid osteomas (OOs) are small, benign but painful bone tumors, mainly observed in children
 and young adults. Pain, almost universal, is characteristically greater at night. Pain is
 well relieved by NSAIDs but resolution is not always complete and pain reappears a few hours
 after the last dose. Also long-term consumption of NSAID can lead to serious adverse events.
 Therefore OOs are usually cured shortly after diagnosis, mainly by means of percutaneous
 treatment (PT) under computed tomography (CT) (radiofrequency coagulation or interstitial
 laser ablation).

 The clinical success rate using these techniques is 96% at 6-month, 94% at 24-month. However,
 the technique is not distributed everywhere since it is performed by highly specialized
 interventional radiologists. The PT is performed under general, spinal or regional
 anesthesia. General anesthesia is used in most cases, especially in children. When the OO is
 located in close proximity to the skin, cartilage, vessels and nerves, severe complications
 may occur and additional procedures such as infusion of saline or injection of CO2 at the
 interface between the OO and the vulnerable structure are done. Also few anatomic locations
 are not accessible to a PT.

 The natural history of OOs remains poorly understood. However investigators in small series
 of conservatively treated OOs suggested a spontaneous healing of the lesion with
 mineralization of the nidus and resolution of pain (mean duration of pain in patients with
 NSAID treatment: 33 months NSAID).

 The efficacy of bisphosphonates on pain related to benign (Langherhans cell histiocytosis,
 fibrous dysplasia, Paget disease) or malignant bone lesions has been widely reported. The
 investigators observed such efficacy in a small series of 20 patients with percutaneously
 hard-to-reach or recurrent OO using one to three infusions of zoledronate. The clinical
 efficacy assessed on pain relief was accompanied by a significantly increased mineralization
 of the nidus. The investigators postulated that bisphosphonates had accelerated the natural
 history of OO.

 Our hypothesis is that three infusions of zoledronate (4mg) repeated monthly in patients with
 symptomatic OO is non-inferior to percutaneous treatment on the efficacy, measured by pain
 relief at Visual Analogical Scale (VAS).

 The main objective of this randomized study is to demonstrate that in patients with OO,
 treatment with three intravenous cycles of 4mg of zoledronic acid administered monthly, is
 non-inferior to treatment with percutaneous thermal ablation on the efficacy measured by the
 percentage of pain relief between baseline and end of treatment.

 NB: Patients for whom the OO would not be percutaneously accessible (that is to say when the
 percutaneous treatment or surgical excision destruction expose the patient to a substantial
 risk in terms of neurologic or joint damages) will be offered to participate in a cohort,
 only in Lariboisière and Cochin hospital in Paris. In the cohort, the clinical follow-up will
 be conducted as it is currently proposed in Laribosisière hospital (no act added by the
 research). Objectives of the register will be explained to the patient. It consists in
 collecting anonymized medical data after a bisphosphonate treatment to statuate on the
 efficacy of the bisphosphonates to relieve pain due to osteoid osteoma.

 Study design of the randomized study:

 -  Selection / Inclusion visit: verification of eligibility, randomization and recollection
 of patient consent.

 -  Intervention:

 -  percutaneous thermal ablation at V1 visit (i.e. maximum one month after the
 selection / inclusion visit)

 -  or three zoledronic acid infusions at V1, V2 (one month after v1) and V3 visits
 (one month after V2)

 -  V4 visit at 4 months (end of treatment, evaluation of the main outcome) and V7 visit at
 16 months (end of study, evaluation of the secondary outcomes).

 -  Option: One to 3 additional visits (V4, V5 and V6) for zoledronic acid infusion can be
 proposed to the patient, depending on the efficacy of the previous infusion.
Inclusion Criteria:

 -  Age superior or equal to 10 years

 -  Patient with a typical osteoid osteoma diagnosed on clinical and radiological criteria
 (MRI and scanner), validated by a binomial clinician / radiologist.

 -  OO never treated or in treatment failure, or recurrent OO.

 -  OO percutaneously accessible

 -  Pain intensity is superior or equal to 40 mm on a VAS at inclusion visit.

 -  Written informed consent signed by the patient or his representative (for minors,
 agreement of the child and signature of the two mandatory parents).

 -  Patient affiliated to the social security.

 Exclusion Criteria:

 -  Patients with other diseases or receiving treatment that may impact on bone tissue or
 its metabolism.

 -  Patients suffering from renal failure (i.e. lower than 60 ml/min according to the
 Cowcroft equation).

 -  Patients with severe hepatocellular insufficiency (TP<50%).

 -  Patients with a history of iritis or uveitis.

 -  Patient with untreated rickets or osteomalacia.

 -  Patient with untreated dental infection or planed dental surgery during the study
 period.

 -  Patient with untreated infection of the external auditory canal (ex: furuncle, eczema
 superinfection)

 -  Patient already treated by bisphosphonates.

 -  Patients with hypersensitivity to the active substance, to other bisphosphonates or to
 any of the excipients (List of excipients: mannitol (E421), sodium citrate (E331),
 water for injections).

 -  Patient enrolled in another biomedical research protocol and during the whole study

 -  Pregnant or breastfeeding women, or planning pregnancy during the course of the study

 -  Women of child bearing potential (women following menarche and until post-menopause)
 and sexually active, without an effective contraceptive measure during the period of
 treatment (hormonal contraception or mechanical contraception)*

 * Oral contraceptive methods include:

 -  combined (oestrogen and progestogen containing) hormonal contraception associated with
 inhibition of ovulation (oral, intravagina or transdermal)

 -  progestogen-only hormonal contraception associated with inhibition of ovulation (oral,
 intravagina or transdermal).

 -  Mechanical methods of contraception include intrauterine device and intrauterine
 hormone-releasing system.Patient enrolled in another biomedical research protocol
 and during the whole study

 Patients who would not meet the inclusion criteria "OO percutaneously accessible" will be
 offered to participate in a register, only in Lariboisière hospital. This register will
 target specifically children aged of at least 12 years old and adults.