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

## TL;DR

Weekly teriparatide treatment reduces bone microdamage in ovariectomized monkeys, improving bone quality and fracture resistance.

## Contribution

Demonstrates that weekly teriparatide reduces microdamage in trabecular bone by restoring collagen cross-link balance, independent of bone mass.

## Key findings

- OVX monkeys had significantly higher microdamage compared to controls.
- Weekly teriparatide reduced microdamage and improved collagen cross-link profiles.
- Microdamage reduction correlated more with non-enzymatic cross-link decrease than bone volume increase.

## Abstract

Background/purpose: Osteoporosis is commonly treated with daily or weekly teriparatide, yet its impact on microdamage accumulation - a critical contributor to bone fragility - remains insufficiently evaluated in animal models. We evaluated the effects of weekly teriparatide on microdamage in tibial trabecular bone and examined its associations with bone mass, structure, turnover, and collagen cross-linking in ovariectomized (OVX) cynomolgus monkeys.

Methods: Seventy-seven adult female cynomolgus monkeys were randomized into four groups (n = 18-20 each): sham-operated, OVX + vehicle, and OVX + weekly teriparatide at 1.2 μg/kg or 6.0 μg/kg. After 18 months, proximal tibiae and iliac crest specimens were harvested. Tibial trabecular sections were assessed for histomorphometry, microdamage (crack density, crack surface density), and collagen cross-linking. Iliac crest samples were analyzed for bone turnover indices.

Results: The OVX group showed significantly higher microdamage accumulation compared to all other groups. Weekly teriparatide administration effectively prevented microdamage accumulation and improved collagen cross-link profile. Regression analysis revealed that reductions in microdamage correlated more strongly with decreased non-enzymatic pentosidine cross-links than with increases in trabecular 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 gain. This suggests that teriparatide enhances bone quality and resistance to fracture via modulation of bone matrix integrity.