Advertisement

Bone histomorphometry in three females with Rett syndrome

      Abstract

      The frequent occurrence of osteoporosis in Rett syndrome raises questions about the etiology of this finding. It is unknown whether there is any relationship between low bone mass and the underlying genetic disorder. We recently had an opportunity to study the status of bone remodeling by quantitative bone histomorphometry in three girls ages 9.75, 13.5, and 14 years, with typical Rett syndrome who required scoliosis surgery.
      Anterior iliac crest bone biopsies were performed 1–2 days after double labeling of the bone surfaces with tetracycline. Samples were processed for plastic embedding, sectioned, stained, and histomorphometry performed in the cancellous bone. The same observer performed all measurements. Bone volume was reduced, surface parameters of formation (osteoid surface) were normal while parameters of resorption (osteoclast surface and number) were decreased. The rate of bone formation was reduced in the first two girls but could not be measured in the third girl due to lack of double labeling. It may be that the slow rate of bone formation seen in each age group impedes the development and accumulation of peak bone mass and contributes to the decreased bone volume associated with Rett syndrome, although the data is limited.
      This is the first report to document decreased bone volume determined by quantitative bone histomorphometry in patients with Rett syndrome. With the recent identification of MECP2 mutations in Rett syndrome it is quite likely that genetic factors not only play a major role in brain development but may also influence other organ growth including bone formation.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Armstrong D.D.
        The neuropathology of Rett syndrome – overview.
        Neuropediatrics. 1994; 26: 100-104
        • Haas R.H.
        • Dixon S.D.
        • Sartoris D.
        • Hennessy M.J.
        Osteopenia in Rett syndrome.
        J Pediatr. 1997; 13: 771-774
        • Leonard H.
        • Thomson M.R.
        • Glasson E.J.
        • Fyfe S.
        • Leonard S.
        • Bower C.
        • et al.
        A population based approach to the investigation of osteopenia in Rett syndrome.
        J Dev Med and Child Neurol. 1999; 41: 323-328
        • Schultz R.J.
        • Glaze D.G.
        • Motil K.J.
        The pattern of growth failure in Rett syndrome.
        Am J Dis Child. 1993; 147: 633-637
        • Amir R.E.
        • Van den Veyer I.B.
        • Wan M.
        • Tran C.Q.
        • Francke U.
        • Zogbi H.Y.
        Rett syndrome is caused by mutations in X-linked MECP-2, encoding methyl-CpG-binding protein 2.
        Nat Genet. 1999; 23: 185-188
        • Prestwood K.M.
        • Gunness M.
        • Muchmore D.B.
        • Lu Y.
        • Wong M.
        • Raisz L.G.
        A comparison of the effects of raloxifene and estrogen on bone in postmenopausal women.
        J Clin Endocrinol Metab. 2000; 85: 2197-2202
        • Baron R.
        • Vignery A.
        • Neff L.
        • Silverglate A.
        • Santa Maria A.
        Processing of undecalcified bone specimens for bone histomorphometry.
        in: Recker R.R. Bone histomorphometry: techniques and interpretation. CRC Press, Boca Raton, FL1983: 13-35
        • Parfitt A.M.
        • Drezner M.K.
        • Glorieux F.H.
        • Kanis J.A.
        • Malluche H.
        • Meunier P.J.
        • et al.
        Bone histomorphometry: standardization of nomenclature, symbols, and units.
        J Bone Miner Res. 1987; 2: 595-610
        • Glorieux F.H.
        • Travers R.
        • Taylor A.
        • Bowen J.R.
        • Rauch F.
        • Norman M.
        • et al.
        Normative data for iliac bone histomorphometry in growing children.
        Bone. 2000; 26: 103-109
        • Kleerekoper M.
        • Avioli L.V.
        Osteopenia, pathogenesis and therapy.
        in: Avioli L.V. Krane M. Metabolic bone disease and clinically related disorders. 3rd ed. Academic Press, San Diego1998: 387-409
        • Marolagas S.C.
        Birth and death of bone cells: basic regulatory mechanisms and implications for pathogenesis and treatment of osteoporosis.
        Endocr Rev. 2000; 21: 115-137
        • Julu P.O.O.
        • Kerr A.M.
        • Hansen S.
        • Apartopoulos F.
        • Jamal G.A.
        Functional evidence of brain stem immaturity in Rett syndrome.
        Eur Child Adolesc Psychiatry. 1997; 6: 47-54
      1. Armstrong DD. Presentation at the World Congress on Rett syndrome 2000.

        • Porges S.W.
        Vagal tone: a physiological marker of stress vulnerability.
        Pediatrics. 1992; 90: 498-504
        • Bregeon C.
        • Renier J.C.
        Further vascular, bone and autonomic investigations in algodystrophy.
        Acta Orthop Belg. 1998; 64: 77-87