Lead induced differences in bone properties in osteocalcin +/+ and -/- female mice

Area of Science:

• Bone biology and toxicology
• Skeletal health and aging
• Mineral metabolism

Background:

• Lead (Pb) toxicity is a significant health concern, with bone serving as its primary reservoir.
• Lead negatively affects bone remodeling and is linked to fractures in the elderly.
• Osteocalcin (OC) is vital for bone remodeling and fracture resistance, declining with age and certain diseases.

Purpose of the Study:

• To investigate the impact of lead exposure on bone mineral properties in osteocalcin-depleted mice.
• To elucidate the interplay between lead toxicity and osteocalcin deficiency in bone remodeling and biomechanics.

Main Methods:

• Comparison of control and lead-exposed (2-6 months) femora from wild-type (OC+/+) and osteocalcin-knockout (OC-/-) mice.
• Utilized Fourier Transform Infrared Imaging (FTIRI), Micro-computed tomography (uCT), and biomechanical testing.
• Analyzed serum turnover markers (P1NP, CTX) to assess bone remodeling.

Main Results:

• Lead exposure increased bone turnover in both OC+/+ and OC-/- mice, altering volumetric and marrow properties.
• Lead decreased mineral/matrix ratio in OC+/+ but increased it in OC-/- mice, also increasing crystallinity in OC-/-.
• Lead-exposed osteocalcin-knockout mice showed increased bone formation and cross-sectional area but reduced collagen maturity, confirming osteocalcin's role in coupling formation and resorption.

Conclusions:

• Lead exposure exacerbates bone turnover and compromises bone strength, particularly in the absence of osteocalcin.
• Osteocalcin plays a critical role in maintaining bone strength, even at low lead exposure levels, suggesting reduced osteocalcin contributes to fracture risk in the elderly.
• Combined effects of aging, low-level lead exposure, and reduced osteocalcin levels may significantly increase fracture risk.