title: Fluorotoxic metabolic bone disease: an osteo-renal syndrome caused by excess fluoride ingestion in the tropics.
abstract: BACKGROUND
  There is scant data available on the pathogenetic mechanisms of varied clinical presentation of bone disease in patients with excess fluoride ingestion in the Indian subcontinent. The present study is comprehensive and state of the art, incorporating all essential elements of bone mineral metabolism in patients with excess fluoride ingestion.
  
  
  METHODS
  We studied 24 patients (age 31 +/- 16 years) with fluorotoxic metabolic bone disease (FMBD) for their clinical, radiological and biochemical parameters like serum calcium, phosphorous, alkaline phosphatase (SAP), 25-hydroxyvitamin D, 1,25 dihydroxyvitamin D, and parathyroid hormone levels, nephrologic parameters that assess renal handling of calcium and phosphorous and skeletal dynamics as revealed by bone histomorphometry.
  
  
  RESULTS
  Major clinical manifestations were bone pain (79%), Tetany (12.5%) and dental mottling (38%). Radiological findings included osteosclerosis (96%), pseudofracture and ligamentous calcification (50%). These patients manifested hypocalcemia and raised SAP with normal serum phosphorus. There was a positive correlation between serum creatinine and phosphorous excretion index (PEI) and a negative correlation between declining endogenous creatinine clearance (Cr.Cl) and increasing renal loss of calcium and phosphorus as indicated by increased calcium to creatinine ratio and PEI. Bone histomorphometry revealed impairment of primary mineralization with hypomineralized lacunae, interstitial mineralization defects and very thick and extended osteoid seams. Autopsy findings in a patient who died of azotemia showed tubular atrophy with secondary glomerular changes.
  
  
  CONCLUSIONS
  Fluoride intoxication plays an important role in the pathogenesis of the unique osteo-renal syndrome.
authors.affiliation: Department of Endocrinology and Metabolism, Sri Venkateswara Institute of Medical Sciences, Tirupati-517 507, Andhra Pradesh, India. cvhari5endo@rediffmail.com <cvhari5endo@rediffmail.com>
authors.forename: C V
authors.initials: CV
authors.lastname: Harinarayan
authors.forename: N
authors.initials: N
authors.lastname: Kochupillai
authors.forename: S V
authors.initials: SV
authors.lastname: Madhu
authors.forename: N
authors.initials: N
authors.lastname: Gupta
authors.forename: P J
authors.initials: PJ
authors.lastname: Meunier
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D005459:Fluorides / Q000008:administration & dosage*; D006801:Humans; D007194:India; D007668:Kidney / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D011859:Radiography; D013577:Syndrome; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; C104450:25-hydroxyvitamin D; D003404:Creatinine; D000469:Alkaline Phosphatase; D005459:Fluorides; D002118:Calcium