Weekly Teriparatide Treatment Decreases Microdamage in Tibial Trabecular Bone of Ovariectomized Cynomolgus Monkeys

Area of Science:

• Bone Biology and Disease
• Pharmacology and Therapeutics
• Skeletal Tissue Engineering

Background:

• Osteoporosis treatment often involves daily or weekly teriparatide, but its effect on microdamage accumulation, a key factor in bone fragility, is not well understood in animal models.
• Microdamage accumulation is a critical contributor to bone fragility.

Purpose of the Study:

• To evaluate the effects of weekly teriparatide on microdamage in the tibial trabecular bone of ovariectomized (OVX) cynomolgus monkeys.
• To examine the associations between teriparatide treatment, microdamage, bone mass, structure, turnover, and collagen cross-linking.

Main Methods:

• Seventy-seven adult female cynomolgus monkeys were randomized into sham-operated, OVX + vehicle, and OVX + weekly teriparatide (1.2 or 6.0 μg/kg) groups.
• After 18 months, tibiae and iliac crests were harvested for histomorphometry, microdamage assessment (crack density, crack surface density), collagen cross-linking analysis, and bone turnover indices.

Main Results:

• Ovariectomized monkeys exhibited significantly higher microdamage accumulation compared to control groups.
• Weekly teriparatide administration effectively prevented microdamage accumulation and improved the collagen cross-link profile.
• Reductions in microdamage strongly correlated with decreased non-enzymatic pentosidine cross-links, more so than with increased bone volume or enzymatic cross-links.

Conclusions:

• Weekly teriparatide administration attenuates tibial trabecular bone microdamage by restoring collagen cross-link balance, independent of bone mass.
• Teriparatide enhances bone quality and fracture resistance by modulating bone matrix integrity.