Abstract
IntroductionPathological calcium-containing crystals accumulating in the joints, synovial fluid, and soft tissues are noted in most elderly patients, yet arthritic crystal formation remains idiopathic. Interestingly, elevated lactic acid and bone erosion are frequently among the comorbidities and clinical features of patients with highest incidence of crystal arthropathies. This work shows that bone particulates (modeling bone erosion) dissolve in lactic acid and directly generate crystals, possibly presenting a mechanism for crystal accumulation in osteoarthritis.Methods and resultsMicronized human bone (average particle size of 160 μm x 79 μm) completely dissolved in lactic acid in 48 hours, and in synovial fluid with 500 mMol lactic acid in 5 days, generating birefringent rhomboid and rod-shaped crystals. SEM analysis with energy dispersive x-ray spectroscopy of these crystals showed average dimensions of around 2 μm x 40 μm, which contained oxygen, calcium and phosphorous at 8.64:1.85:1. Raman spectroscopy of the generated crystals further showed 910/cm and 1049/cm peaks, aligning with calcium oxalate monohydrate and calcium pyrophosphate, respectively.ConclusionsThis work shows that lactic acid and micronized mineralized bone together directly generate calcium-containing crystals. These observations may provide insights into the elusive etiology of arthritis with crystal involvement, possibly indicating lactic acid as a clinical target for treatment.
Highlights
Pathological calcium-containing crystals accumulating in the joints, synovial fluid, and soft tissues are noted in most elderly patients, yet arthritic crystal formation remains idiopathic
Pathological calcium and phosphate containing crystals in osteochondral regions of joints, in the surround joint soft tissue and in synovial fluid are commonly noted in most forms of osteoarthritis[5,6]
The dissolved rhomboid and rodshaped crystals from bone exhibited positive birefringence in both 500mMol lactic acid in human synovial fluid (Fig 1D), and formed crystals with micronized bone directly dissolved into 85% lactic acid (Fig 1E and 1F), comparable to control diseased synovial fluid with crystals (Fig 1B)
Summary
Pathological calcium-containing crystals accumulating in the joints, synovial fluid, and soft tissues are noted in most elderly patients, yet arthritic crystal formation remains idiopathic. Elevated lactic acid and bone erosion are frequently among the comorbidities and clinical features of patients with highest incidence of crystal arthropathies. This work shows that bone particulates (modeling bone erosion) dissolve in lactic acid and directly generate crystals, possibly presenting a mechanism for crystal accumulation in osteoarthritis
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