Time-dependent changes in skeletal response to teriparatide: escalating vs. constant dose teriparatide (PTH 1-34) in osteoporotic women.
Once-daily injections of teriparatide initially increase biochemical markers of bone formation and resorption, but markers peak after 6-12 months and then decline despite continued treatment. We sought to determine whether increasing teriparatide doses in a stepwise fashion could prolong skeletal responsiveness. We randomized 52 postmenopausal women with low spine and/or hip bone mineral density (BMD) to either a constant or an escalating subcutaneous teriparatide dose (30 μg daily for 18months or 20 μg daily for 6 months, then 30 μg daily for 6 months, and then 40 μg daily for 6 months). Serum procollagen I N-terminal propeptide, osteocalcin, and C-terminal telopeptide of type I collagen were assessed frequently. BMD of the spine, hip, radius, and total body was measured every 6 months. Acute changes in urinary cyclic AMP in response to teriparatide were examined in a subset of women in the constant dose group. All bone markers differed significantly between the two treatment groups. During the final six months, bone markers declined in the constant dose group but remained stable or increased in the escalating dose group (all markers, p<0.017). Nonetheless, mean area under the curve did not differ between treatments for any bone marker, and BMD increases were equivalent in both treatment groups. Acute renal response to teriparatide, as assessed by urinary cyclic AMP, did not change over 18 months of teriparatide administration. In conclusion, stepwise increases in teriparatide prevented the decline in bone turnover markers that is observed with chronic administration without altering BMD increases. The time-dependent waning of the response to teriparatide appears to be bone-specific.
Massachusetts General Hospital Department of Medicine, Endocrine Unit, Boston, MA 02114, USA. ewyu@partners.org
Elaine W
EW
Yu
Robert M
RM
Neer
Hang
H
Lee
Jason J
JJ
Wyland
Amanda V
AV
de la Paz
Melissa C
MC
Davis
Makoto
M
Okazaki
Joel S
JS
Finkelstein
D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects*; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy*; D010349:Patient Compliance; D017698:Postmenopause; D019379:Teriparatide / Q000008:administration & dosage / Q000627:therapeutic use*
D050071:Bone Density Conservation Agents; D019379:Teriparatide; D000242:Cyclic AMP