title: Bone histomorphometry before and after long-term treatment with cinacalcet in dialysis patients with secondary hyperparathyroidism.
abstract: The multicenter, single-arm BONAFIDE study characterized the skeletal response to cinacalcet in adult dialysis patients with plasma parathyroid hormone (PTH) levels of 300 pg/ml or more, serum calcium of 8.4 mg/dl or more, bone-specific alkaline phosphatase over 20.9 ng/ml and biopsy-proven high-turnover bone disease. Of 110 enrolled patients, 77 underwent a second bone biopsy with quantitative histomorphometry after 6-12 months of cinacalcet treatment. The median PTH decreased from 985 pg/ml at baseline to 480 pg/ml at the end of study (weeks 44-52). Bone formation rate/tissue area decreased from 728 to 336 μm(2)/mm(2)/day, osteoblast perimeter/osteoid perimeter decreased from 17.4 to 13.9%, and eroded perimeter/bone perimeter decreased from 12.7 to 8.3%. The number of patients with normal bone histology increased from none at baseline to 20 at 12 months. Two patients had adynamic bone at the end of study with a PTH under 150 pg/ml, and one patient with overt hypophosphatemia at baseline that reoccurred during follow-up developed osteomalacia. Thus, long-term treatment with cinacalcet substantially reduced PTH, diminished the elevated bone formation rate/tissue area, lowered several biochemical markers of high-turnover bone disease toward normal, and generally improved bone histology. Twenty patients had normal bone histology at follow-up, whereas most had mild hyperparathyroidism or mixed uremic osteodystrophy.
authors.affiliation: Laboratory of Pathophysiology, University of Antwerp, Wilrijk, Belgium.
authors.forename: Geert J
authors.initials: GJ
authors.lastname: Behets
authors.affiliation: Department of Nephrology, University of Skopje, Skopje, Macedonia.
authors.forename: Goce
authors.initials: G
authors.lastname: Spasovski
authors.affiliation: Amgen Inc., Thousand Oaks, California, USA.
authors.forename: Lulu R
authors.initials: LR
authors.lastname: Sterling
authors.affiliation: Amgen Inc., Thousand Oaks, California, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Goodman
authors.affiliation: Amgen Inc., Thousand Oaks, California, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Spiegel
authors.affiliation: Emeritus Professor of Medicine, University of Antwerp, Wilrijk, Belgium.
authors.forename: Marc E
authors.initials: ME
authors.lastname: De Broe
authors.affiliation: Laboratory of Pathophysiology, University of Antwerp, Wilrijk, Belgium.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: D'Haese
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000209:etiology / Q000473:pathology*; D001862:Bone Resorption / Q000097:blood; D057966:Calcimimetic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood; D000069449:Cinacalcet / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000097:blood; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000628:therapy; D013997:Time Factors; D055815:Young Adult
chemical_list: D057966:Calcimimetic Agents; D010281:Parathyroid Hormone; D000469:Alkaline Phosphatase; D002118:Calcium; D000069449:Cinacalcet