Parenteral pamidronate prevents thyroid hormone-induced bone loss in rats.
Pamidronate (APD) is a bisphosphonate that prevents bone loss from a variety of causes. We studied the role of APD in preventing thyroid hormone-induced bone loss. A total of 32 rats were assigned to one of four treatment groups: (1) -APD/triiodothyronine (-T3), (2) -APD/+T3, (3) +APD/-T3, or (4) +APD/+T3. In the first of two studies, the rats received APD for the first week and T3 for the second week, and then their blood was analyzed for alkaline phosphatase and osteocalcin. Alkaline phosphatase and osteocalcin were significantly higher (p < 0.05) in hyperthyroid rats (-APD/+T3, 3.9 +/- 0.25 mukat/liter and 23 +/- 1.6 nM, respectively) than in control animals (2.53 +/- 0.28 mukat/liter and 18.3 +/- 1.4 nM, respectively). Hyperthyroid rats pretreated with APD (+APD/+T3) had levels of alkaline phosphatase and osteocalcin no different from controls. In a second study, rats were divided into the same four groups, except they received APD/placebo and T3/placebo concomitantly for 3 weeks. At the end of the study, bone mineral density (BMD) of the femur, spine, and whole body was measured by dual-energy x-ray absorptiometry, and the calcium content of the femora was measured directly. In hyperthyroid rats (-APD/+T3) BMD was significantly lower than in controls in the spine (0.201 +/- 0.004 versus 0.214 +/- 0.002 g/cm2, p < 0.05) and femur (0.204 +/- 0.003 versus 0.218 +/- 0.002, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Rosen
H N
HN
Charles A. Dana Research Institute, Boston, Massachusetts.
Sullivan
E K
EK
Middlebrooks
V L
VL
Zeind
A J
AJ
Gundberg
C
C
Dresner-Pollak
R
R
Maitland
L A
LA
Hock
J M
JM
Moses
A C
AC
Greenspan
S L
SL
D015502:Absorptiometry, Photon; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000139:chemically induced / Q000517:prevention & control*; D002118:Calcium / Q000032:analysis; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005269:Femur / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D006980:Hyperthyroidism / Q000150:complications; D008297:Male; D015675:Osteocalcin / Q000097:blood; D000077268:Pamidronate; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D014284:Triiodothyronine / Q000633:toxicity*
D004164:Diphosphonates; D014284:Triiodothyronine; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D000077268:Pamidronate; D002118:Calcium