Fibrous dysplasia (FD) is a rare disorder wherein scar tissue replaces normal bone-tissue, weakens the bone, causing deformity and intense pain. We present 2 cases of FD due to McCune Albright Syndrome (MAS) showing remarkable clinical improvement with pamidronate.

An 8 year-old girl presented with excessive weight gain since 3 years after fracture of right tibia/fibula following a trivial trauma; early fatigue, generalized bone pains and inability to bear weight due to extreme right leg pain. She weighed 45 kg with body mass index of 26.6 kg/m2. Her height was 118 cm. She had multiple café-au-lait spots and bilateral genu valgum. Her pubertal status was B2P1A1M0, indicating early puberty. Serum calcium (9.6 mg/dL), phosphorus (4.8 mg/dL), parathyroid hormone (42 pg/mL, normal range: 9-65 pg/mL) and 25-hydroxyvitamin D (25OHD3) (21 ng/mL, normal range: 12-40 ng/mL) were normal, while alkaline phosphatase (ALP) (609 IU/L) (range: 40-240 IU/L) was high. Skeletal survey showed healing fracture of tibia with distal tibial cystic lesion, generalized osteopenia of foot bones with cortical thinning of leg bones (Fig.1). Radiograph of shoulders revealed patchy sclerotic areas in proximal ends of both humerii with ‘cotton wool’ appearance. The diagnosis of FD was confirmed by MRI of right ankle and Dexa and bone scan (Fig.1).

Fig.1 A: X ray of bilateral tibia and fibula with ankles depicting healing fracture of tibia with distal-tibial cystic lesion with hohmogeneous ground glass matrix and cloud of smoke calcification, generalized osteopenia of foot bones with cortical thinning of leg bones. B: T2 weighted images of MRI depicting heterogenous hyperintensity in distal third of right tibia and small heterogeous hyperintensities in ankle bones. C: A section from computed tomography scan showing ground glass appearance of lower end of tibia. D: Lateral X ray depicting distal tibial cystic lesion, healing fracture and osteopenia of foot bones especially talus and calcaneus.

The second case was a 2 year-old female child with complaints of limping, bony pains, flat foot, and deformity of right ankle since 1 and a half years of age, which gradually progressed to right leg lengthening at presentation to our institute. She weighed 16.6 kg while her length was 82.3 cm. She had multiple café-au-lait spots (>6 mm with irregular borders). Parathyroid hormone levels were 19.6 pg/mL (normal range: 9-65 pg/mL). ALP was 585 IU/L (normal range: 40-240 IU/L) while calcium and phosphorus were 8.5 mg/dL and 4.1 mg/dL, respectively. Nuclear scan showed mildly increased tracer distribution in right tibia and left fibula, suspicious of FD. MRI right leg showed remodeling of proximal third of right tibia with cortical/periosteal thickening and depressed postero-medial bone with focal cortical break in proximal third with surrounding tissue edema. The left fibula also showed remodeling along with periosteal thickening in the middle third.

Both patients were diagnosed as MAS and treated with pamidronate (in view of pain and reduced mobility) 1 mg/kg/day for 3 days given 3 monthly for 6 cycles along with metformin, calcium and vitamin D supplementation with appropriate diet, whereafter they improved. During the administration of pamidronate patients were under continuous electrocardiogram monitoring while vital signs were frequently recorded. Hypocalcemia (biochemical and manifest) was specifically observed. Calcium, phosphorus, ALP, 25OHD3 levels (27.5 ng/mL in case 1 and 32.4 ng/mL in case; normal range: 12-40 ng/mL) were normal at follow-up.

At 2 years follow-up, they showed improvement in pain (assessed by visual analogue scale), mobility, deformity, general well-being and quality of life (ALP improved after 1 year). These 2 patients were able to perform all the activities of daily living appropriate to their age whilst the parents were satisfied with their overall progress. To the best of our knowledge, this is the first report from India describing role of pamidronate in FD due to MAS.

FD is characterized by replacement of normal bone tissue by fibrous connective tissue with a characteristic whorled pattern containing trabeculae of immature non-lamellar bone. Histopathologically, FD shows fibrous stroma with spicules of disconnected woven bone with a few mature osteoblasts and osteoclasts. Biphosphonates inhibit osteoclasts, reduce bone resorption and can lead to refilling of dysplastic lesions.

As observed by most other investigators, our observations highlight that good results can be obtained with pamidronate in FD, which should be administered early to halt disease progression, preserve bone mass, reduce fracture rates, avoid deformities, alleviate symptoms and delay/avoid surgery(1,2). Since standard guidelines for its use are unavailable, therapeutic response to pamidronate is noteworthy while longterm follow-up is awaited(3). Pamidronate therapy appears to be useful in children and adolescents with FD with a good short term safety profile. Potential multisystem (renal, hepatic, cardiovascular, gastrointestinal and skeletal) and oncological adverse effects of long term use are open to observation and speculation(4,5).