Bone tissue and its mineralization in aged estrogen-depleted rats after long-term intermittent treatment with parathyroid hormone (PTH) analog SDZ PTS 893 or human PTH(1-34)

Intermittently administered parathyroid hormone (PTH) is a potent bone anab olic agent, We aimed to determine the impact of long-term treatment with PT H on bone structure, dynamics, and mineralization. We ovariectomized (ovx) 1-year-old rats with the exception of a baseline and a sham-operated group. Twelve weeks later, a 36 week treatment with PTH analog SDZ PTS 893 (12.5, 25, 50, 100 mug/kg), human PTH(1-34) (25, 50, 100 mug/kg), or vehicle (ovx , sham) was initiated. Bone dynamics, structure, and mineralization were ev aluated in the lumbar spine and in the femoral diaphysis, Cancellous bone t urnover was elevated 12 weeks postovariectomy in estrogen-deficient, vehicl e-treated animals, but returned to the level of the sham group by 48 weeks, The animals experienced substantial cancellous bone loss associated with a reduction of trabecular number and presented with a partly rod-like trabec ular network. After 36 weeks of treatment with SDZ PTS 893 or human PTH(1-3 4), cancellous bone formation rates and turnover were raised in all treated groups compared with age-matched controls, The mineral apposition rate was increasing with dose, This amplified matrix synthesis led to trabecular th ickening, but not to an increase in trabecular number, resulting in a crude , plate-like cancellous network with a high hone volume fraction. Fluorochr ome label-based cortical bone dynamics demonstrated that a thick ring of ne w bone was formed at the endocortex by activation of modeling drifts during treatment, Treatment-induced cortical bone formation was increased with do se at the subperiosteal and endocortical envelopes, but substantially highe r at the latter, Intracortical bone turnover was elevated near the endocort ex, Bone mineralization was undisturbed in all compartments. The average de gree of mineralization was lowered slightly, reflecting the increased porti on of new bone Formed during treatment. In summary, the main anabolic effec t was mediated for both peptides by an increase in bone apposition with dos e, persisting throughout treatment that lasted more than one third of the l ifespan of the rats, and direct activation of bone-forming surfaces. As a r esult, a substantial amount of new bone, maintained at elevated turnover an d adequate mineralization levels, formed predominantly at compartments expo sed to bone marrow. (Bone 28:237-250; 2001) (C) 2001 by Elsevier Science In c, All rights reserved.