title: Osteoporotic vertebral fractures during pregnancy: be aware of a potential underlying genetic cause.
abstract: BACKGROUND
  Although the baby growing in its mother's womb needs calcium for skeletal development, osteoporosis and fractures very rarely occur during pregnancy.
  
  
  METHODS
  A 27-year-old woman in the seventh month of her first pregnancy contracted midthoracic back pain after lifting an object. The pain was attributed to her pregnancy, but it remained postpartum. Her past medical history was uneventful, except for severely reduced vision of her left eye since birth. Family history revealed that her maternal grandmother had postmenopausal osteoporosis and her half-brother had three fractures during childhood after minor trauma. Her height was 1.58 m; she had no blue sclerae or joint hyperlaxity. Laboratory examination including serum calcium, phosphate, alkaline phosphatase, creatinine, β-carboxyterminal cross-linking telopeptide of type I collagen, 25-hydroxyvitamin D, and TSH was normal. Multiple thoracic vertebral fractures were diagnosed on x-ray examination, and dual-energy x-ray absorptiometry scanning showed severe osteoporosis (Z-scores: L2-L4, -5.6 SD; femur neck, -3.9 SD). DNA analyses revealed two compound heterozygous missense mutations in LRP5. The patient's mother carried one of the LRP5 mutations and was diagnosed with osteoporosis. Her half-brother, treated with cabergoline for a microprolactinoma, also had osteoporosis of the lumbar spine on dual-energy x-ray absorptiometry and carried the same LRP5 mutation. The patient was treated with risedronate for 2.5 years. Bone mineral density and back pain improved. She stopped bisphosphonate use 6 months before planning a second pregnancy.
  
  
  CONCLUSIONS
  Our patient was diagnosed with osteoporosis pseudoglioma syndrome/familial exudative vitreoretinopathy. Potential underlying genetic causes should be considered in pregnancy-associated osteoporosis with implications for patients and relatives. More studies regarding osteoporosis treatment preceding conception are desirable.
authors.affiliation: Department of Internal Medicine (N.C.-O., L.O., M.C.Z.), Erasmus MC, 3015 CE Rotterdam, The Netherlands; Department of Human Genetics (L.H.H.), Radboud Medical Center, 6500 HC Nijmegen, The Netherlands; Department of Internal Medicine (R.M.K.), Albert Schweitzer Hospital, 3318 AT Dordrecht, The Netherlands; and Departments of Ophthalmology (C.C.W.K.) and Clinical Genetics (M.E.H.S.), Erasmus MC, 3015 CE Rotterdam, The Netherlands.
authors.forename: Natalia
authors.initials: N
authors.lastname: Campos-Obando
authors.forename: Ling
authors.initials: L
authors.lastname: Oei
authors.forename: Lies H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: Rosalie M
authors.initials: RM
authors.lastname: Kiewiet
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.forename: Marleen E H
authors.initials: ME
authors.lastname: Simon
authors.forename: M Carola
authors.initials: MC
authors.lastname: Zillikens
mesh_terms: D000328:Adult; D000080345:Familial Exudative Vitreoretinopathies; D005260:Female; D006801:Humans; D010013:Osteogenesis Imperfecta / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D010024:Osteoporosis / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D058866:Osteoporotic Fractures / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree; D011247:Pregnancy; D011248:Pregnancy Complications / Q000175:diagnosis* / Q000235:genetics; D016103:Spinal Fractures / Q000150:complications* / Q000235:genetics; D018630:Vitreoretinopathy, Proliferative / Q000150:complications / Q000175:diagnosis* / Q000235:genetics