Effect of recombinant human parathyroid hormone (1-84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial.
BACKGROUND
Recombinant human parathyroid hormone (1-84) (PTH) increases bone mass and strength and improves bone quality by stimulating new bone formation.


OBJECTIVE
To determine the safety of PTH and its effect on the incidence of vertebral fractures in postmenopausal women with osteoporosis.


METHODS
18-month, randomized, double-blind, placebo-controlled, parallel-group study.


METHODS
168 centers in 9 countries.


METHODS
2532 postmenopausal women with low bone mineral density at the hip or lumbar spine.


METHODS
Women received 100 mug of recombinant human PTH or placebo daily by subcutaneous injection. All received calcium, 700 mg/d, and vitamin D3, 400 U/d.


METHODS
New or worsened vertebral fractures (primary outcome) and changes in bone mineral density and safety (secondary outcomes).


RESULTS
67.2% of patients who received at least 1 dose of the study drug completed the study. Parathyroid hormone reduced the risk for new or worsened vertebral fractures, but in sensitivity analyses, the magnitude of the reduction was changed with assumptions about fracture incidence in patients who did not complete the study (relative risk assuming no fractures, 0.42 [95% CI, 0.24 to 0.72] [P = 0.001]; relative risk assuming fracture incidence observed in all patients who completed the trial, 0.60 [CI, 0.36 to 1.00] [P = 0.05]; relative risk assuming fracture incidence observed in the placebo group, 0.62 [CI, 0.37 to 1.04] [P = 0.07]). Compared with placebo, mean bone mineral density increased at the spine by 6.9% (CI, 6.4% to 7.4%) and at the hip by 2.1% (CI, 1.7% to 2.5%) but decreased at the forearm in the PTH-treated group. Parathyroid hormone treatment increased the percentage of participants with hypercalciuria, hypercalcemia, and nausea by 24% (CI, 20% to 27%), 23% (CI, 21% to 26%), and 14% (CI, 11% to 16%), respectively, compared with placebo.


CONCLUSIONS
Baseline serum PTH and vitamin D levels were not measured. Many patients discontinued the trial prematurely.


CONCLUSIONS
Parathyroid hormone (1-84) reduced the overall risk for new or worsened vertebral fracture in postmenopausal women with osteoporosis. Hypercalciuria, hypercalcemia, and nausea were more common in women who took the drug. Although the magnitude of the reduction was sensitive to assumptions about fracture incidence in patients who did not complete the study, the findings suggest that PTH provides an alternative therapeutic option for fracture prevention.
Greenspan
Susan L
SL
University of Pittsburgh, Osteoporosis Prevention and Treatment Center, Pittsburgh, Pennsylvania 15213, USA.
Bone
Henry G
HG
Ettinger
Mark P
MP
Hanley
David A
DA
Lindsay
Robert
R
Zanchetta
Jose R
JR
Blosch
Consuelo M
CM
Mathisen
Annette L
AL
Morris
Stephen A
SA
Marriott
Thomas B
TB
D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced; D053565:Hypercalciuria / Q000139:chemically induced; D015994:Incidence; D008159:Lumbar Vertebrae / Q000293:injuries; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012306:Risk; D012680:Sensitivity and Specificity; D016103:Spinal Fractures / Q000453:epidemiology / Q000517:prevention & control*
D015415:Biomarkers; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D000469:Alkaline Phosphatase