The in vitro effect of pH on osteoclasts and bone resorption in the cat: Implications for the pathogenesis of FORL

Abstract

Dental disease due to osteoclast over-activity reaches epidemic proportions in older domestic cats and has also been reported in wild cats. Feline osteoclastic resorptive lesions (FORL) involve extensive resorption of the tooth leaving it liable to root fracture and subsequent tooth loss. The aetio-pathogenesis of FORL is not known. Recent work has shown that systemic acidosis causes increased osteoclast activation and that loci of infection or inflammation in cat mouth are likely to be acidotic. To investigate this, we generated osteoclasts from cat blood and found that they formed in large numbers (approximately 400) in cultures on bovine cortical bone slices. Acidosis caused an increase in the size of cells-in cultures maintained up to 14 days at basal pH 7.25, mean osteoclast area was 0.01 +/- 0.003 mm(2), whereas an 8.6-fold increase was observed in cells cultured between 11 and 14 days at pH 7.15 (0.086 +/- 0.004 mm(2)). Acidosis caused a modest increase in the number of osteoclasts. Exposure to pH 6.92 exhibited a 5-fold increase in the area of bone slices covered by resorption lacunae ( approximately 70% bone slice resorbed). In line with this finding, significant increases were observed in the expression of cathepsin K and proton pump enzymes (both approximately 3-fold) that are key enzymes reflective of resorptive activity in osteoclasts. These results demonstrate that acidosis is a major regulator of osteoclast formation and functional activation in the cat, and suggest that local pH changes may play a significant role in the pathogenesis of FORL.

Dental Health and Diet

“…34,40 In addition to dietary influences in oral pH, bacterial populations associated with chronic inflammatory disease in the cat's mouth may contribute to an acidic microenvironment necessary for the tooth decalcification that occurs with resorptive lesions. Other signs include oral malodor, gingivitis, and excessive salivation.…”

“…14 In addition, cats that had their teeth cleaned at least twice a week and were fed diets containing higher levels of magnesium, calcium, phosphorus, and potassium were less likely to develop oral lesions. 86 However, research demonstrating a direct relationship between a cat's diet, metabolic acid-base balance, and the development of FORLs is lacking. Although limited data are available, a positive association has also been reported between resorptive lesions and feeding noncommercial (homemade) diets, cat treats, table foods, and diets containing low amounts of calcium or high amounts of vitamin D. [80][81][82] The increased use of acid sprays as a coating on dry cat foods and of urine-acidifying diets for the prevention of struvite urolithiasis in cats led to speculation that some commercial cat foods may reduce the oral pH and promote an environment that is favorable for tooth demineralization.…”

Promotion of osteoclast differentiation and activation in spite of impeded osteoblast-lineage differentiation under acidosis: Effects of acidosis on bone metabolism

“…It has been unclear where acidosis acts in the course of osteoclast formation, although there have been several reports that acidosis exerts promotive effects on osteoclastogenesis (13,14). We investigated this point to demonstrate that acidosis primarily acts on osteoclast differentiation in the last stage of the process, just before large-scale cell fusion ( Figures 3A and 3B) (15).…”

Biomechanical aspect of feline dental resorptive lesions formation

“…Alternate succession of tensile and compressive stresses leads to focal ischemia, biochemical alterations and subsequent resorptions. Recent studies of Muzylak et al (2006Muzylak et al ( , 2007 revealed that hypoxic conditions ans local hypoxia in the tooth environment may play a role in the pathogenesis of feline dental resorptive lesions. Harvey et al (2004) also speculated that either event, tearing of the periodontal ligament collagen fibers or exposing the rough cellular pre-cementum as a result of cement microcracs could stimulate a local microscopic concentration of cytokines.…”