Calcium-Containing Crystal-Associated Arthropathies in the Elderly
In contrast to gout, there is no specific target therapy for lowering CPP crystal load in the elderly. Crucial in the management of CPPD in the elderly is the search for associated diseases, such as hyperparathyroidism, hemochromatosis, hypomagnesemia, and hypophosphatemia, as well as avoidance of tacrolimus, which facilitates or causes CC.16 Correction of the underlying metabolic disorder, especially when undertaken early, may reduce the severity of CPPD. However, there is little evidence to suggest that treatment of associated disease results in resolution of CPPD—most famously, although therapeutic phlebotomy does not help in hemochromatosis for prevention of crystal disease, chelating agents do seem to be moderately effective.26 Only oral administration of magnesium has shown a reduction in meniscal CC in a patient with CPPD arthropathy.27 In addition, this was in the setting of familial hypomagnesemia associated CPPD. However, unlike uricosuric agents for gout, no pharmacologic treatments can prevent CPPD crystal formation and deposition in tissues.
Therapeutic Agents
Magnesium
Magnesium is a cofactor for the activity of pyrophosphatases that converts inorganic pyrophosphates (PPis) into orthophosphates. In addition, magnesium can increase the solubility of CPP crystals. Early detection and management of hypomagnesemia are recommended, because it occurs in patients who have well-defined conditions and situations: Gitelman syndrome, thiazide and loop diuretics use, tacrolimus use, familial forms of renal magnesium wasting or use of proton pump inhibitors, short bowel syndrome, and intestinal failure in patients receiving home parenteral nutrition. Long-term administration of magnesium in some patients with chronic hypomagnesemia decreased meniscal calcification.27-29
Dietary Calcium
Epidemiologic studies showed a lower incidence of CC in Chinese subjects. The authors of the study speculate that this lower prevalence of CPPD could result from high levels of calcium found in the drinking water in Beijing, which may affect parathyroid hormone secretion.30 Further studies are needed to confirm this hypothesis, as it could be a cheaper approach to pseudogout prevention.
Probenecid
Probenecid is an in vitro inhibitor of the transmembrane PPi transporter thought to possibly prevent extracellular PPi elaboration. However, this observation has not been confirmed by either case reports or clinical trials.31
Phosphocitrate
Phosphocitrate acts directly on preventing crystal deposition in tissues in CPPD as well as BCP based on in vitro evidence and mouse models.32,33
Hyaluronan
An amelioration of pain and increased range of motion were observed in radiographic CC with OA.34 However, it is associated with increased acute CPP arthritis.35
Radiosynovectomy
In a double-blind study of 15 patients with symmetrical CPPD arthropathy, the knee that underwent intra-articular injection of yttrium-90 (5 mCi) plus steroid had less pain, stiffness, joint line tenderness, and effusion compared with the contralateral control knee injected with saline and steroids.36
Precipitators of Acute Pseudogout
Diuretics are known to exacerbate gout, but they also can exacerbate pseudogout. A recent case-control study nested within a United Kingdom general practice database found that loop diuretics rather than hydrochlorothiazide was associated with increased risk of CPPD mediated primarily by magnesium reabsorption in the loop of Henle.28 Chronic kidney disease associated with secondary and tertiary hyperparathyroidism increases calcium or PPi concentration, which leads to CPP-crystal deposition.
In addition, multiple case reports have described acute pseudogout caused by bisphosphonate administration for osteoporosis or Paget disease—more likely in the elderly population. Intravenous pamidronate, oral etidronate, and alendronate therapy have all been described in the elderly.37 The overall mechanism behind this link is not completely understood, but bisphosphonates are structurally similar to PPi. Pseudogout attacks also have been described in neutropenic patients undergoing treatment with granulocyte-colony stimulating factor.38 In addition to pharmaceutical exacerbation of pseudogout, surgical procedures and trauma can precipitate attacks. Joint lavage has been described to increase the incidence of pseudogout.39 It was hypothesized that joint lavage with fluid induced “crystal shedding” from CPPD crystals imbedded in the joint tissue. Patients who underwent meniscectomy of the knee 20 years ago had a 20% incidence of CC in the knee that was operated compared with 4% CC in the contralateral nonoperated knee.40 Overall, the surgery most linked with a pseudogout attack, however, is parathyroidectomy.41
Basic Calcium Phosphate Crystals
Basic calcium phosphate crystals are common but rarely diagnosed due to the cumbersome and expensive methods required to identify these crystals.42 
