Pamidronate prevents bone loss and decreased bone strength in adult female and male rats fed an isocaloric low-protein diet.
Isocaloric dietary protein deficiency is associated with decreased BMD and bone strength as well as depressed somatotroph and gonadotroph axis. Inhibition of increased bone resorption by the bisphosphonate pamidronate in rats fed an isocaloric low-protein diet fully prevents bone loss and alteration of bone strength.


BACKGROUND
Isocaloric dietary protein deficiency is associated with decreased BMD and bone strength as well as depressed somatotroph and gonadotroph axis. This negative bone balance is the consequence of increased bone resorption and decreased bone formation. Whether inhibition of bone resorption could prevent low-protein diet-induced bone loss and alteration of biomechanics is not known.


METHODS
The effect of the bisphosphonate pamidronate was studied in 5.5-month-old female or 6-month-old male rats pair-fed a control (15% casein) or an isocaloric low-protein (2.5% casein) diet for 19 and 26 weeks, respectively. Pamidronate (0.6 mg/kg) was given subcutaneously 5 days/month for 4 months in female rats or for 5 months in male rats. BMD, microarchitecture, and bone strength were measured at the level of the proximal and midshaft tibia. Urinary deoxypyridinoline excretion, serum osteocalcin, and IGF-I were also measured.


RESULTS
The increase in bone resorption in female rats (+100%) and in male rats (+33%) fed a low-protein diet was prevented by pamidronate treatment. The reduced osteocalcin levels observed in rats fed a low-protein diet were further decreased in both female (-34%) and male (-30%) rats treated with pamidronate. The bone turnover decrease induced by pamidronate prevented bone strength reduction, trabecular bone loss, microarchitecture, and BMD alterations induced by the isocaloric low-protein diet. Similar effects were observed at the level of the midshaft tibia. Significant decrease of plasma IGF-I was observed in rats fed a low-protein diet independently of the pamidronate treatment.


CONCLUSIONS
In conclusion, inhibition of increased bone resorption in rats fed an isocaloric low-protein diet fully prevents bone loss and alteration of bone strength.
Mekraldi
Samia
S
Service of Bone Diseases WHO Collaborating Center for Osteoporosis Prevention, Department of Rehabilitation and Geriatrics, University Hospital of Geneva, Geneva, Switzerland.
Toromanoff
Anne
A
Rizzoli
René
R
Ammann
Patrick
P
D000596:Amino Acids / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism; D018753:Diet, Protein-Restricted; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D000077268:Pamidronate; D011859:Radiography; D051381:Rats; D013977:Tibia / Q000000981:diagnostic imaging
D000596:Amino Acids; D015415:Biomarkers; D004164:Diphosphonates; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; C036020:deoxypyridinoline; D000077268:Pamidronate