title: Variability in the measured response of bone to teriparatide.
abstract: Apparent failures of bone mineral density (BMD) response to teriparatide at spine or hip occur even in a high compliance context (15% spine and 55% hip). Apparent non-responders nevertheless show good biomarker response, suggesting that apparent BMD non-response is due to measurement imprecision. Calcium intake may be an important determinant of hip response.
  
  
  BACKGROUND
  Individuals vary in response to bone active agents, but that variability is poorly quantified and its basis is not well understood. The study included 203 postmenopausal women with moderately severe osteoporosis, all treated with teriparatide, calcium, and vitamin D. The study was performed at the Creighton University Medical Center, a single site.
  
  
  METHODS
  This is a prospective study of change in bone mineral density and resorption biomarkers over a 12-month treatment period. BMD response at spine and total hip was quantified by computing slopes for each participant's values, and biomarker change by the difference in values across the 12-month study period.
  
  
  RESULTS
  Of the total number of participants, 85.2% exhibited a significant spine BMD response, while only 44.8% had a significant change at the hip. However, mean biomarker response was marginally larger for the BMD non-responders at either site than for the responders, indicating biological, if not measurable densitometric, activity of teriparatide in essentially all participants.
  
  
  CONCLUSIONS
  Occasional apparent failures of BMD response in patients receiving teriparatide are probably not due to failure of response at the level of the bone remodeling apparatus, but instead reflect a combination of measurement imprecision and variable bone remodeling balance. The reason for the latter remains unclear.
authors.affiliation: Creighton University Medical Center, 601 N 30th Street, Suite 4841, Omaha, NE 68131, USA. rheaney@creighton.edu
authors.forename: R P
authors.initials: RP
authors.lastname: Heaney
authors.forename: P
authors.initials: P
authors.lastname: Watson
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000652:urine; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects; D024042:Collagen Type I / Q000652:urine; D005260:Female; D006621:Hip Joint / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000503:physiopathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000503:physiopathology* / Q000652:urine; D010455:Peptides / Q000652:urine; D011446:Prospective Studies; D019379:Teriparatide / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D019379:Teriparatide; D006909:Hydroxyproline
references.citation: N Engl J Med. 2001 May 10;344(19):1434-41
references.pmid: 11346808
references.citation: Am J Clin Nutr. 2010 Jul;92(1):101-5
references.pmid: 20484446
references.citation: J Bone Miner Res. 2003 Mar;18(3):539-43
references.pmid: 12619939
references.citation: Ann Intern Med. 2007 Mar 6;146(5):326-39
references.pmid: 17339618
references.citation: Clin Chim Acta. 1970 Feb;27(2):347-9
references.pmid: 5417233
references.citation: Osteoporos Int. 2005 Jul;16(7):842-8
references.pmid: 15580479
references.citation: J Bone Miner Res. 2003 Jan;18(1):9-17
references.pmid: 12510800
references.citation: N Engl J Med. 2005 Aug 11;353(6):555-65
references.pmid: 16093464
references.citation: J Bone Miner Res. 2009 Jun;24(6):1125-31
references.pmid: 19113918
references.citation: J Bone Miner Res. 2009 Apr;24(4):726-36
references.pmid: 19049337
references.citation: J Clin Endocrinol Metab. 2003 Nov;88(11):5212-20
references.pmid: 14602752
references.citation: J Assoc Physicians India. 2008 Jun;56:418-24
references.pmid: 18822620