Use of 18F-Fluoride Positron Emission Tomography in the Assessment and Evaluation of Therapy in Monostotic Paget's Disease of Bone

I. Background of the subject:

Paget's disease of bone is a condition characterized by a focal exuberant increase in bone remodeling, resulting in a number of important architectural abnormalities, potentially leading to bone deformity and bone fragility. This condition may be polyostotic or monostotic. Biological markers of bone remodeling, mainly alkaline phosphatase and markers of bone resorption such as urinary hydroxyproline, are commonly utilized to assess Paget's disease activity.

However, a monostotic Paget's disease is most frequently accompanied by biological markers still in the normal range (1). Conventional 99mTc MDP bone scan is able to localize the lesion. However, the changes observed with this technique after therapy and when the disease recurs do not help much to guide the clinician (3). Indeed, there can be some improvement on the conventional bone scans whereas on the X-ray films, worsening of the pagetic lesions might simultaneously be observed (4). The recurrence of the condition could also be missed by conventional bone scans (4). Therefore, PET scan using 18 Fluoride should by its metabolic approach be able to demonstrate the local activity of Paget's disease, to assess the efficacy of active drugs and to evidence the local recurrence of the disease, better than the conventional existing techniques.

II. Experimental approach and methods

1. 20 patients suffering from a Paget's disease of bone (polyostotic: n = 6; monostotic: n = 14) will be studied prior to and after 1, 6, and 12 months of bisphosphonate therapy. The polyostotic cases will serve to the preliminary feasibility study. A localized Paget's disease will include isolated Pagetic lesions in bones of the face and or the skull, the spine and of the (lower or upper) limbs.
2. Paget's disease confirmed by X rays will be quantified by biological parameters of bone remodeling: total alkaline phosphatase, bone specific alkaline phosphatase, serum C-telopeptide (CTX), urinary NTx corrected by creatinine in a morning spot urine after an overnight fast.
3. Routine biological parameters such as creatinine, full blood count, serum calcium, phosphate and magnesium, as well as 25OH vitamin D, 1,25(OH)2 vitamin D and iPTH will also be performed at the start and after therapy. A total duration of 5 years should be considered for the completion of the whole study. 18 Fluoride will be produced by the cyclotron, localized in Louvain-la-Neuve (Belgium).