The diuretic indapamide increases bone mass and decreases bone resorption in spontaneously hypertensive rats supplemented with sodium.
Clinical and epidemiological studies suggest that thiazide diuretics can prevent bone loss and decrease the incidence of hip fractures. However, the mechanism of the effect of diuretics on bone is not clearly established. Indapamide (IDP), a sulfonamide diuretic related to thiazides, is used to treat hypertension. Sixty spontaneously hypertensive rats (SHRs) were divided into four groups and treated with or without IDP (1.5 mg/kg/day) during 8 weeks in the presence or absence of a high sodium load (8% NaCl supplementation in the diet). Sodium and calcium excretions were increased in the rats receiving the high sodium load (SHR + 8% NaCl) comparatively with control rats (SHR). IDP decreased and increased, respectively, calcium and sodium excretions. Serum parathyroid hormone (PTH) was unchanged in any group. Bone density was measured at the femur, tibia, and vertebrae, and bone morphometry was performed at the metaphysis of the femur to evaluate bone architecture. Rats fed a high sodium diet had an average 5.5% decreased bone density at every site except the femoral diaphysis. The trabecular bone volume was also decreased (SHR + 8% NaCl vs. SHR, 11.99+/-0.78 vs. 17.51+/-1.5%, p < 0.05). An increase in trabecular separation suggested that these changes were due to increased bone resorption. In the SHR + 8% NaCl + IDP group, IDP increased bone density and trabecular bone volume (SHR + 8% NaCl + IDP vs. SHR + 8% NaCl, 16.52+/-1.04 vs. 11.99+/-0.78%, p < 0.05). Trabecular separation and pyridinoline/creatinine excretion (SHR + 8% NaCl + IDP vs. SHR + 8% NaCl, 136.39+/-9.62 vs. 195.18+/-22.34 nmol/mmol, p < 0.05) were also decreased by IDP. These results show that in rats receiving a high sodium diet, IDP can reverse sodium-induced bone loss and increased bone resorption independently of changes in serum PTH.
Lalande
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A
INSERM U349, Hôpital Lariboisière, Paris, France.
Roux
C
C
Graulet
A M
AM
Schiavi
P
P
De Vernejoul
M C
MC
D015502:Absorptiometry, Photon; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000188:drug therapy; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D007190:Indapamide / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D012965:Sodium Chloride; D013131:Spine / Q000000981:diagnostic imaging / Q000187:drug effects; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects
D000959:Antihypertensive Agents; D015415:Biomarkers; D004232:Diuretics; D012965:Sodium Chloride; D007190:Indapamide