SEARCH

SEARCH BY CITATION

The McCune-Albright syndrome is characterized by sexual precocity, large and rough-bordered café-au-lait spots, and polyostotic fibrous dysplasia due to the mosaic distribution of an activating mutation of the Gsα gene in endocrine and nonendocrine tissues.1,2 In bone, this mutation causes overactive cAMP generation and proliferation of osteoblast progenitors in the bone marrow stroma leading to increased IL-6 synthesis, high levels of c-fos expression, and increased numbers of osteoclasts.3,4 At the advancing margins of the bone lesions, these abnormally stimulated osteoclasts cause expansion of the bony lesions, pain, and pathologic al fractures.5

In July of 1995, a 22-year-old white woman presented with the McCune-Albright syndrome and severe pain in her left hip that required her to use crutches. DEXA of the hip (A) and plain films (B) showed an expanding lesion with a thin cortex and a profound decrease in bone mineral density (BMD). She was treated with four 90 mg infusions of intravenous pamidronate given at three to four week intervals from July to September 1995 and a calcium supplement. Relief of pain and increased BMD (A) were accompanied by decreased urinary excretion of the N-telopeptide of type I collagen of bone. In December 1995, pain still interfered with ambulation and the N-telopeptide excretion had increased, prompting the use of oral alendronate therapy. With 10 mg/day, the N-telopeptide excretion decreased, and by September 1996, BMD continued to increase. By February 1997, the patient was pain free; internal and external rotation, flexion, and extension of the left hip were normal, as was her unaided gait. In May 1997, total proximal femoral BMD had increased 158% and the lesion showed marked cortical thickening and refilling from the margins (A). Early fractures and deformities typical of the McCune-Albright syndrome need not occur since this previously medically untreatable bone disease is now amenable to aminobisphosphonate therapy.6

thumbnail image

Figure  . X-ray of the hip shows the ground-glass appearance of the destructive lesion. Note how well the image was captured by the DEXA study in A.

Download figure to PowerPoint

thumbnail image

Figure  . X-ray of the hip shows the ground-glass appearance of the destructive lesion. Note how well the image was captured by the DEXA study in A.

Download figure to PowerPoint

REFERENCES

  1. Top of page
  2. REFERENCES
  • 1
    Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM 1991 Activating mutations of the stimulatory G protein in the McCune-Albright syndrome N Engl J Med 325:16881695; 1738-1740 (editorial).
  • 2
    Shenker A, Weinstein LS, Sweet DE, Spiegel AM 1994 An activating Gsα mutation is present in fibrous dysplasia of bone in the McCune-Albright syndrome J Clin Endocrinol Metab 79:750755.
  • 3
    Yamamoto T, Ozono K, Kasayama S, Yoh K, Hiroshima K, Takagi M, Matsumoto S, Michigami T, Yamaoka K, Kishimoto T, Okada S 1996 Increased IL-6 production by cells isolated from the fibrous bone dysplasia tissues in patients with McCune-Albright syndrome J Clin Invest 98:3035.
  • 4
    Candeliere GA, Glorieux FH, Prud'homme J, St.-Arnaud R 1995 Increased expression of the c-fos proto-oncogene in bone marrow from patients with fibrous dysplasia N Engl J Med 352:15461551.
  • 5
    Kaplan FS, Fallon MD, Boden SD, Schmidt R, Senior M, Haddad JG 1988 Estrogen receptors in bone in a patient with polyostotic fibrous dysplasia (McCune-Albright syndrome) N Engl J Med 319:421425.
  • 6
    Liens D, Delmas PD, Meunier PJ 1994 Long-term effects of intravenous pamidronate in fibrous dysplasia of bone Lancet 343:953954.