Download PDF
Semin Musculoskelet Radiol 2002; 06(4): 285-298
DOI: 10.1055/s-2002-36727
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Drug-Induced Metabolic Bone Disorders

Jack Lawson
  • Department of Radiology, Yale University School of Medicine, New Haven, Connecticut
Further Information

Publication History

Publication Date:
22 January 2003 (online)

Also available at
    Permissions and Reprints

ABSTRACT

A number of drugs, either physician prescribed or those taken without the knowledge of the physician, may have metabolic effects on, and result in abnormal changes in, the musculoskeletal system. These medications may involve the developing fetus, infant, child, or adult and may manifest as drug-induced embryopathies, osteoporosis, osteomalacia, or rickets, or a combination of these, or they may be associated with proliferative changes. Not uncommonly, the radiologist may be the first physician to identify the metabolic manifestations of these medications. The radiological changes associated with such drugs will be reviewed. Certain drugs may have teratogenic effects, nonteratogenic effects, or both. These effects, dependent solely on the timing of administration, will be discussed separately.

KEYWORD

Congenital abnormality,osteoporosis - rickets - osteomalacia - periostitis - proliferative enthesopathy

REFERENCES

  • 1 Forfar J O, Nelson M M. Epidemiology of drugs taken by pregnant women: drugs that may affect the fetus adversely.  Clin Pharmacol Ther . 1973;  14 632-642
    PubMedGoogle Scholar
  • 2 McBride W G. Thalidomide and congenital abnormalities.  Lancet . 1961;  2 1358
    PubMedGoogle Scholar
  • 3 McCredie J, McBride W G. Some congenital abnormalities: possibly due to embryonic peripheral neuropathy.  Clin Radiol . 1973;  24 204-211
    CrossrefPubMedGoogle Scholar
  • 4 McCredie J, Willert H G. Longitudinal limb deficiencies and the sclerotomes. An analysis of 378 dysmelic malformations induced by thalidomide.  J Bone Joint Surg Br . 1999;  81 9-23
    CrossrefPubMedGoogle Scholar
  • 5 Rocha J. Thalidomide given to women in Brazil.  BMJ . 1994;  308 1061
    PubMedGoogle Scholar
  • 6 American Academy of Pediatrics Committee on Drugs. Anticonvulsants and pregnancy.  Pediatrics . 1979;  63 331-333
    PubMedGoogle Scholar
  • 7 Jick S S, Terris B Z. Anticonvulsants and congenital malformations.  Pharmacotherapy . 1997;  17 561-564
    PubMedGoogle Scholar
  • 8 Canger R, Battino D, Canevini M P. Malformations in offspring of women with epilepsy: a prospective study.  Epilepsia . 1991;  40 1231-1236
    PubMedGoogle Scholar
  • 9 Waziri M, Ionasescu V, Zellweger H. Teratogenic effect of anticonvulsant drugs.  Am J Dis Child . 1976;  130 1022-1023
    PubMedGoogle Scholar
  • 10 Wood P B, Young L W. Pseudo-hyperphalangism in fetal dilantin syndrome.  Radiology . 1979;  131 371-372
    PubMedGoogle Scholar
  • 11 Robinson P B, Harvey W, Belal M S. Inhibition of cartilage growth by the anticonvulsant drugs diphenylhydantoin and sodium valproate.  Br J Exp Pathol . 1988;  69 17-22
    PubMedGoogle Scholar
  • 12 Lammer E J, Chen D T. Retinoic acid embryopathy.  N Engl J Med . 1985;  313 837-841
    CrossrefPubMedGoogle Scholar
  • 13 Bagheri M M, Burd L, Martsolf J T, Klug M G. Fetal alcohol syndrome: maternal and neonatal characteristics.  J Perinat Med . 1998;  26 263-269
    PubMedGoogle Scholar
  • 14 Jones K L, Smith D W, Ulleland C N. Patterns of malformation in offspring of alcoholic mothers.  Lancet . 1973;  1267-1269
    PubMedGoogle Scholar
  • 15 Maroteaux P, Lavollay B, Bomsell F. Chondrodysplasia punctata and maternal alcohol intoxication.  Arch Fr Pediatr . 1984;  41 547-550
    PubMedGoogle Scholar
  • 16 Iosub S, Fuchs M, Bingol N. Incidence of major congenital malformations in offsprings of alcoholics and polydrug users.  Alcohol . 1985;  2 521-523
    CrossrefPubMedGoogle Scholar
  • 17 Milunsky A, Graef J W, Gaynor Jr F M. Methotrexate-induced congenital malformations.  J Pediatr . 1968;  72 790-795
    CrossrefPubMedGoogle Scholar
  • 18 Buckley L M, Bullaboy C A, Leichtman L, Marquez M. Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of the mother.  Arthritis Rheum . 1997;  40 971-973
    CrossrefPubMedGoogle Scholar
  • 19 Viscarello R R, Ferguson D D, Nores J, Hobbins J C. Limb-body wall complex associated with cocaine abuse: further evidence of cocaine's teratogenicity.  Obstet Gynecol . 1992;  80 523-526
    PubMedGoogle Scholar
  • 20 Hannig V L, Phillips III A J. Maternal cocaine abuse and fetal anomalies: evidence for teratogenic effects of cocaine.  South Med J . 1991;  84 498-499
    PubMedGoogle Scholar
  • 21 Fourie D T, Hay I T. Warfarin as a possible teratogen.  S Afr Med J . 1975;  49 2081-2083
    PubMedGoogle Scholar
  • 22 Lamontagne J M, Leclerc J E, Carrier C, Bureau M. Warfarin embryopathy.  J Otolaryngol . 1984;  13 127-129
    PubMedGoogle Scholar
  • 23 Hall J G, Pauli R M, Wilson K M. Maternal and fetal sequelae of anticoagulation during pregnancy.  Am J Med . 1980;  68 122-140
    CrossrefPubMedGoogle Scholar
  • 24 Sparber M. Diagnostically confusing complications of diphenylhydantoin therapy.  Ann Intern Med . 1963;  59 914-930
    PubMedGoogle Scholar
  • 25 Leonidas J, Brill P W, Waldman N. Antiepileptic therapy and rickets in children.  Radiology . 1973;  109 409-412
    PubMedGoogle Scholar
  • 26 Lifschitz F, Maclaren N K. Vitamin D-dependent rickets in institutionalized mentally retarded children receiving long-term anticonvulsant therapy: a survey of 288 patients.  J Pediatr . 1973;  83 612-620
    PubMedGoogle Scholar
  • 27 Dent C E, Richens A, Rowe D JF, Stamp T CB. Osteomalacia with long-term anticonvulsant therapy in epilepsy.  BMJ . 1970;  4 69-72
    PubMedGoogle Scholar
  • 28 Tolman K G, Jubiz W, Sannella J. Osteomalacia associated with anticonvulsant drug therapy in mentally retarded children.  Pediatrics . 1975;  56 45-51
    PubMedGoogle Scholar
  • 29 O'Hare J A, Duggan B, O'Driscoll B, Callaghan N. Biochemical evidence for osteomalacia with carbamazepine therapy.  Acta Neurol Scand . 1980;  62 282-286
    PubMedGoogle Scholar
  • 30 Stamp T CB. Drug and chemical-induced rickets (and osteomalacia). In: Preger L, ed. Induced Disease: Drug, Irradiation, Occupation New York: Grune & Stratton 1980: 27-43
    Google Scholar
  • 31 Addy P. Rickets associated with anticonvulsant therapy in children with tuberous sclerosis.  Arch Dis Child . 1997;  51 972-974
    PubMedGoogle Scholar
  • 32 Mallette L E. Acetazolamide-accelerated anticonvulsant osteomalacia.  Arch Intern Med . 1973;  137 1013-1017
    PubMedGoogle Scholar
  • 33 Campbell J E, Tam C S, Sheppard H H. "Brown tumor" of hyperparathyroidism induced with anticonvulsant medication.  J Can Assoc Radiol . 1977;  28 73-76
    PubMedGoogle Scholar
  • 34 McCrea E S, Rao C V, Diaconis J N. Roengtenographic changes during long-term diphenylhydantoin therapy.  South Med J . 1980;  73 312-317
    PubMedGoogle Scholar
  • 35 Kattan K R. Calvarial thickening after dilantin medication.  AJR Am J Roentgenol . 1970;  110 102-105
    PubMedGoogle Scholar
  • 36 Harris M, Goldhaber P. Root abnormalities in epileptics and the inhibition of parathyroid hormone induced bone resorption by diphenylhydantoin in tissue culture.  Arch Oral Biol . 1974;  19 981-984
    PubMedGoogle Scholar
  • 37 Kattan K R. Thickening of the heel-pad associated with long-term dilantin therapy.  AJR Am J Roentgenol . 1975;  124 52-56
    PubMedGoogle Scholar
  • 38 De Virgiliis S, Congia M, Frau F. Deferoxamine-induced growth retardation in patients with thalassemia major.  J Pediatr . 1988;  113 666-669
    PubMedGoogle Scholar
  • 39 Brill P W, Winchester P, Giardina P J, Cunningham-Rundles S. Deferoxamine-induced bone dysplasia in patients with thalassemia major.  AJR Am J Roentgenol . 1991;  156 561-565
    PubMedGoogle Scholar
  • 40 Orzincolo C, Scutellari P N, Castaladi G. Growth plate injury of the long bones in treated β-thalassemia.  Skeletal Radiol . 1992;  21 39-44
    PubMedGoogle Scholar
  • 41 Chan Y, Li C, Chu W C, Cheng J C, Chik K W. Deferoxamine-induced bone dysplasia in the distal femur and patella of pediatric patients and young adults: MR imaging appearance.  AJR Am J Roentgenol . 2000;  175 1561-1566
    PubMedGoogle Scholar
  • 42 Chan Y L, Li C K, Pang L M, Chik K W. Deferoxamine-induced long bone changes in thalassemic patients-radiographic features, prevalence and relations with growth.  Clin Radiol . 2000;  55 610-614
    CrossrefPubMedGoogle Scholar
  • 43 Nagant de Deuxchaisnes C, Rombouts-Lindemans C, Huaux J P. Paget's disease of bone.  BMJ . 1981;  283 1054-1055
    PubMedGoogle Scholar
  • 44 Wood B J, Robinson G C. Drug induced changes in myositis ossificans progressiva.  Pediatr Radiol . 1976;  5 40-43
    CrossrefPubMedGoogle Scholar
  • 45 Gallacher S J, Boyle I T, Capell H A. Pseudogout associated with the use of cyclical etidronate therapy.  Scott Med J . 1991;  36 49
    PubMedGoogle Scholar
  • 46 van Dyke J J, Falkson H C, van der Merve M A. Unexpected toxicity in patients treated with iphosphamide.  Cancer Res . 1972;  32 921-924
    PubMedGoogle Scholar
  • 47 Sweeney L E. Hypophosphatemic rickets after ifosfamide treatment in children.  Clin Radiol . 1993;  47 345-347
    PubMedGoogle Scholar
  • 48 Heaf J G, Nielsen L P. Serum aluminium in haemodialysed patients: relation to osteodystrophy, encephalopathy and aluminium hydroxide consumption.  Miner Electrolyte Metab . 1984;  10 345-350
    PubMedGoogle Scholar
  • 49 Mjoberg B. Aluminium-induced hip fractures: a hypothesis.  J Bone Joint Surg Br . 1989;  71 538
    PubMedGoogle Scholar
  • 50 Freundlich M, Zilleruelo G, Abitol C. Infant formula as a cause of aluminium toxicity in neonatal uraemia.  Lancet . 1985;  2 527-529
    PubMedGoogle Scholar
  • 51 Andreoli S P, Smith J A, Bergstein J M. Aluminum bone disease in children: radiographic features from diagnosis to resolution.  Radiology . 1985;  156 663-667
    PubMedGoogle Scholar
  • 52 Hernandez R J, Sedman A B, Smid D M, Goodman W G. Radiographic manifestations of experimental aluminum toxicity in growing bone.  Skeletal Radiol . 1987;  16 209-215
    CrossrefPubMedGoogle Scholar
  • 53 Llewellyn C H, Resnik C S, Brower A C. Case report 288.  Skeletal Radiol . 1984;  12 223-226
    CrossrefPubMedGoogle Scholar
  • 54 Greenwood R H, Prunty F TG, Silver J. Osteomalacia after prolonged glutethimide administration.  BMJ . 1973;  1 643-645
    PubMedGoogle Scholar
  • 55 Lamm C I, Norton K I, Murphy R JC, Wilkins I A, Rabinowitz J G. Congenital rickets associated with magnesium sulfate infusion for tocolysis.  J Pediatr . 1980;  113 1078-1082
    PubMedGoogle Scholar
  • 56 Brodie M J, Boobis A R, Dollery C T. Rifampicin and vitamin D metabolism.  Clin Pharmacol Ther . 1980;  27 810-814
    PubMedGoogle Scholar
  • 57 Heaton K W, Lever J V, Barnard D. Osteomalacia associated with cholestyramine therapy for postiliectomy diarrhoea.  Gastroenterology . 1972;  62 642-646
    PubMedGoogle Scholar
  • 58 Frame B, Guing H L, Frost H M, Reynolds W A. Osteomalacia induced by laxative (phenolphthalein) ingestion.  Arch Intern Med . 1971;  128 794-796
    CrossrefPubMedGoogle Scholar
  • 59 Neumann L, Jenson B G. Osteomalacia from aluminium and magnesium antacids. Report of a case of bilateral hip fracture.  Acta Orthop Scand . 1989;  60 361-362
    PubMedGoogle Scholar
  • 60 Chudley A E, Brown D R, Holzman I R, Sang Oh K. Nutritional rickets in two very low birth weight infants with chronic lung disease.  Arch Dis Child . 1980;  55 687-690
    PubMedGoogle Scholar
  • 61 Binstadt D H, L'Heureux P R. Rickets as a complication of intravenous hyperalimentation in infants.  Pediatr Radiol . 1978;  7 211-214
    PubMedGoogle Scholar
  • 62 Gefter W B, Epstein D M, Anday E K, Dalinka M K. Rickets presenting as multiple fractures in premature infants on hyperalimentation.  Radiology . 1982;  142 371-374
    PubMedGoogle Scholar
  • 63 Sambrook P N, Birmingham J, Kempler S. Corticosteroid effects on proximal bone femur bone loss.  J Bone Miner Res . 1990;  5 1211-1216
    PubMedGoogle Scholar
  • 64 Gennair C, Citivelli R. Glucocorticoid-induced osteoporosis.  Clin Rheum Dis . 1986;  12 637-654
    PubMedGoogle Scholar
  • 65 Luengo M, Picado C, Del Rio L. Vertebral fractures in steroid dependent asthma and involutional osteoporosis: a comparative study.  Thorax . 1991;  46 803-806
    PubMedGoogle Scholar
  • 66 Gluck O S, Murphy W A, Hahn T J, Hahn B H. Bone loss in adults receiving alternate day glucocorticoid therapy: a comparison with daily therapy.  Arthritis Rheum . 1981;  24 892-898
    PubMedGoogle Scholar
  • 67 Murray R O. Radiological bone changes in Cushing's syndrome and steroid therapy.  Br J Radiol . 1960;  33 1-19
    PubMedGoogle Scholar
  • 68 Maldague B E, Noel H M, Malghem J. The intravertebral vacuum cleft: a sign of ischaemic vertebral collapse.  Radiology . 1978;  129 23-29
    CrossrefPubMedGoogle Scholar
  • 69 Ragab A H, Frech R S, Vietti T J. Osteoporotic fractures secondary to methotrexate therapy of acute leukemia in remission.  Cancer . 1970;  25 580-585
    PubMedGoogle Scholar
  • 70 Jaffe M D, Willis P W. Multiple fractures associated with long-term sodium heparin therapy.  JAMA . 1965;  193 152-154
    PubMedGoogle Scholar
  • 71 Caffey J. Chronic poisoning due to excess of vitamin A.  AJR Am J Roentgenol . 1951;  65 12-26
    PubMedGoogle Scholar
  • 72 Pittsley R A, Yoder F W. Retinoid hyperostosis: skeletal toxicity associated with long-term administration of 13-cis-retinoic acid for refractory ichthyosis.  N Engl J Med . 1983;  308 1012-1014
    PubMedGoogle Scholar
  • 73 Lawson J P, McGuire J. The spectrum of skeletal changes associated with long-term administration of 13-cis-retinoic acid.  Skeletal Radiol . 1987;  16 91-97
    CrossrefPubMedGoogle Scholar
  • 74 Di Giovanna J J, Helffgott R K, Gerber L H, Peck G L. Extraspinal tendon and ligament calcification associated with long-term therapy with etretinate.  N Engl J Med . 1986;  315 1177-1182
    PubMedGoogle Scholar
  • 75 Vilon P, Fiche M, Maugars Y. Sarcome Parosteal du radius apparu lors d'un traitement par etretinate.  Rev Rhum . 1991;  58 825-827
    PubMedGoogle Scholar
  • 76 Elliott R B, Starling M B, Neutze J M. Medical manipulation of the ductus arteriosus.  Lancet . 1975;  1 140-142
    PubMedGoogle Scholar
  • 77 Ueda K, Saito A, Nakano H. Cortical hyperostosis following long-term administration of prostaglandin E1 in infants with cyanotic congential heart disease.  J Pediatr . 1980;  97 834-836
    PubMedGoogle Scholar
  • 78 Hoevels-Guerich H, Haferkorn L, Persigehl M. Widening of cranial sutures after long-term prostaglandin E2 infusion in two newborn infants.  J Pediatr . 1984;  105 72-74
    PubMedGoogle Scholar
  • 79 Teotia S P, Teotia M. Secondary hyperparathyroidism in patients with endemic fluorosis.  BMJ . 1973;  1 637-640
    PubMedGoogle Scholar
  • 80 Schulz E E, Engstrom H, Sauser D D, Baylink D J. Osteoporosis: radiographic detection of fluoride-induced extra-axial bone formation.  Radiology . 1986;  159 457-462
    PubMedGoogle Scholar
  • 81 Gerster J C, Charhon S A, Jaeger P. Bilateral fractures of the femoral neck in patients with moderate renal failure receiving fluoride for spinal osteoporosis.  BMJ . 1983;  287 723-725
    PubMedGoogle Scholar
  • 82 Pak C Y. Fluoride and osteoporosis.  Proc Soc Exp Biol Med . 1989;  191 278-286
    PubMedGoogle Scholar
  • 83 Bregeon C h, Bernat M, Renier J-C, Rebel A, Basile M. Osteose fluoree après 11 ans de traitement ininteruptee par l'acide niflumique.  Nouv Presse Med . 1980;  9 1446-1447
    PubMedGoogle Scholar
      >