Incorporation and distribution of strontium in bone

Area of Science:

• Pharmacokinetics and Bone Metabolism
• Trace Element Distribution in Skeletal Tissues

Background:

• Understanding strontium distribution in bone is crucial for evaluating its therapeutic potential and safety.
• Previous studies have indicated strontium's presence in bone, but detailed distribution patterns and influencing factors require further elucidation.

Purpose of the Study:

• To investigate the distribution and incorporation kinetics of orally administered strontium in bone across different species.
• To identify factors influencing strontium bone levels, including duration of administration, dose, gender, and anatomical site.
• To elucidate the mechanisms of strontium incorporation and elimination from bone.

Main Methods:

• Oral administration of strontium chloride or strontium ranelate to rats, monkeys, and humans.
• Analysis of strontium levels in plasma and bone at various anatomical sites and tissue types (cancellous vs. cortical).
• Assessment of strontium levels following treatment withdrawal to determine clearance rates.

Main Results:

• Strontium incorporation into bone reaches a plateau after prolonged administration (≥4 weeks), with potentially lower levels in females due to absorption differences.
• Steady-state plasma strontium levels are achieved faster than bone levels; bone strontium content varies by anatomical site and bone structure (higher in cancellous and newly formed bone).
• Bone strontium content significantly decreases after treatment withdrawal, consistent with surface exchange and limited ionic substitution mechanisms.

Conclusions:

• Oral strontium incorporation into bone is a time-dependent process influenced by dose, gender, and skeletal site.
• Strontium distribution within bone is heterogeneous, with higher concentrations in newly formed and cancellous bone.
• The primary mechanism of strontium incorporation (surface exchange) explains its rapid elimination from bone upon treatment cessation.