Variability in the measured response of bone to teriparatide.
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.
Heaney
R P
RP
Creighton University Medical Center, 601 N 30th Street, Suite 4841, Omaha, NE 68131, USA. rheaney@creighton.edu
Watson
P
P
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
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
N Engl J Med. 2001 May 10;344(19):1434-41
11346808
Am J Clin Nutr. 2010 Jul;92(1):101-5
20484446
J Bone Miner Res. 2003 Mar;18(3):539-43
12619939
Ann Intern Med. 2007 Mar 6;146(5):326-39
17339618
Clin Chim Acta. 1970 Feb;27(2):347-9
5417233
Osteoporos Int. 2005 Jul;16(7):842-8
15580479
J Bone Miner Res. 2003 Jan;18(1):9-17
12510800
N Engl J Med. 2005 Aug 11;353(6):555-65
16093464
J Bone Miner Res. 2009 Jun;24(6):1125-31
19113918
J Bone Miner Res. 2009 Apr;24(4):726-36
19049337
J Clin Endocrinol Metab. 2003 Nov;88(11):5212-20
14602752
J Assoc Physicians India. 2008 Jun;56:418-24
18822620