OBJECTIVE: To determine the inflammatory potential of basic calcium phosphate (BCP) crystals, which have been identified in human joints. METHODS: Hydroxyapatite, carbonate apatite, whitlockite, and octacalcium phosphate crystals were injected in rat air pouches. Volume and cellularity of the exudate were measured. Physicochemical properties of the injected BCP crystals were determined, and correlations with the magnitude of induced inflammatory responses were sought. RESULTS: Significant differences were observed among the volumes and white blood cell (WBC) counts of the pouch exudates, based on the various crystal types used to induce inflammation. A strong correlation was demonstrated between the specific surface (SS) area of the injected crystals and the area under the curve for induced WBC count versus time (R2 = 0.88, P = 0.05). This correlation was observed for SS area values below 50 m2/gm, but when SS area increased further, this parameter plateaued. Another parameter of inflammatory response was obtained by dividing the area under the curve figuring WBC counts versus time by the corresponding SS area for each crystal type. This parameter increased linearly with the Ca:P ratio (R2 = 0.97, P = 0.0003). CONCLUSION: The inflammatory potential of BCP crystals appeared to vary according to crystal features. SS area and the Ca:P ratio (which correlates with crystal solubility) influenced inflammatory properties. These results could explain the variable clinical consequences of BCP deposits, and must be taken into account in the choice of apatite ceramics for use as biomaterials.
OBJECTIVE: To determine the inflammatory potential of basic calcium phosphate (BCP) crystals, which have been identified in human joints. METHODS:Hydroxyapatite, carbonate apatite, whitlockite, and octacalcium phosphate crystals were injected in rat air pouches. Volume and cellularity of the exudate were measured. Physicochemical properties of the injected BCP crystals were determined, and correlations with the magnitude of induced inflammatory responses were sought. RESULTS: Significant differences were observed among the volumes and white blood cell (WBC) counts of the pouch exudates, based on the various crystal types used to induce inflammation. A strong correlation was demonstrated between the specific surface (SS) area of the injected crystals and the area under the curve for induced WBC count versus time (R2 = 0.88, P = 0.05). This correlation was observed for SS area values below 50 m2/gm, but when SS area increased further, this parameter plateaued. Another parameter of inflammatory response was obtained by dividing the area under the curve figuring WBC counts versus time by the corresponding SS area for each crystal type. This parameter increased linearly with the Ca:Pratio (R2 = 0.97, P = 0.0003). CONCLUSION: The inflammatory potential of BCP crystals appeared to vary according to crystal features. SS area and the Ca:Pratio (which correlates with crystal solubility) influenced inflammatory properties. These results could explain the variable clinical consequences of BCP deposits, and must be taken into account in the choice of apatite ceramics for use as biomaterials.
Authors: Ann K Rosenthal; Mark Fahey; Claudia Gohr; Todd Burner; Irina Konon; Laureen Daft; Eric Mattson; Carol Hirschmugl; Lawrence M Ryan; Peter Simkin Journal: Arthritis Rheum Date: 2008-10