Prevention of estrogen deficiency-related bone loss with human parathyroid hormone-(1-34): a randomized controlled trial.
BACKGROUND
Short-term intermittent administration of parathyroid hormone (PTH) prevents bone loss from the spine in women treated with a gonadotropin-releasing hormone (GnRH) analog. However, the effects of a longer period of PTH administration on bone mass in estrogen-deficient women, particularly on the hip and on cortical bone of the total body, are unknown.


OBJECTIVE
To determine whether more prolonged PTH administration can prevent estrogen deficiency bone loss from the hip, spine, and total body in young women with endometriosis receiving GnRH analog (nafarelin acetate) therapy.


METHODS
Randomized controlled trial.


METHODS
General Clinical Research Center of a tertiary care, university-affiliated hospital.


METHODS
Forty-three women between the ages of 21 and 45 years with symptomatic endometriosis.


METHODS
Nafarelin alone (200 microg intranasally twice daily) or nafarelin plus human parathyroid hormone-(1-34) (hPTH-[1-34]) (40 microg subcutaneously daily).


METHODS
The primary end points were bone mineral density (BMD) of the anterior-posterior and lateral spine, femoral neck, trochanter, radial shaft, and total body at 12 months of treatment.


RESULTS
In the women who received nafarelin alone, the mean (SEM) BMDs of the anterior-posterior spine, lateral spine, femoral neck, trochanter, and total body were 4.9% (0.6%) (P<.001), 4.9% (0.8%) (P<.001), 4.7% (1.1%) (P<.001), 4.3% (0.9%) (P<.001), and 2.0% (0.6%) (P= .003) lower than at baseline after 12 months of therapy. In contrast, coadministration of hPTH-(1-34) increased BMD of the anterior-posterior spine by 2.1% (1.1%) (P=.09) and lateral spine by 7.5% (1.9%) (P=.002) and prevented bone loss from the femoral neck, trochanter, and total body, despite severe estrogen deficiency. Radial shaft BMD did not change significantly in either group. Serum bone-specific alkaline phosphatase and osteocalcin concentrations and urinary excretion of hydroxyproline and deoxypyridinoline increased 2-fold to 3-fold during the first 6 to 9 months of therapy in the women who received nafarelin plus hPTH-(1-34) and then declined. Changes in urinary deoxypyridinolone excretion were strongly predictive (r= 0.85) of changes in spinal BMD in the women who received nafarelin plus hPTH-(1-34).


CONCLUSIONS
Parathyroid hormone prevents bone loss from the proximal femur and total body and increases lumbar spinal BMD in young women with GnRH analog-induced estrogen deficiency.
Endocrine Unit, Massachusetts General Hospital, Boston, Mass 02114, USA. finkelstein@helix.mgh.harvard.edu
J S
JS
Finkelstein
A
A
Klibanski
A L
AL
Arnold
T L
TL
Toth
M D
MD
Hornstein
R M
RM
Neer
D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001774:Blood Chemical Analysis; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling; D004334:Drug Administration Schedule; D004715:Endometriosis / Q000188:drug therapy*; D004967:Estrogens / Q000172:deficiency; D005260:Female; D006728:Hormones / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D017274:Nafarelin / Q000009:adverse effects* / Q000627:therapeutic use; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D019379:Teriparatide / Q000008:administration & dosage / Q000627:therapeutic use*; D016482:Urinalysis
D015415:Biomarkers; D004967:Estrogens; D006728:Hormones; D019379:Teriparatide; D017274:Nafarelin