Systematic review of the evidence underlying the association between mineral metabolism disturbances and risk of fracture and need for parathyroidectomy in CKD.

Background: Chronic kidney disease (CKD) is associated with such complications as fractures and the need for parathyroidectomy. Mineral metabolism control in patients with CKD has been poor. Studies have assessed fractures and parathyroidectomy risk with mineral disturbances, but with considerable diversity in methods. Thus, a systematic review was conducted to assess method or clinical heterogeneity by comparing the design, analytical techniques, and results of studies.

Study Design: Systematic review of the MEDLINE, EMBASE, and Cochrane databases between 1980 and December 2007.

Setting & Population: Patients with CKD or dialysis patients.

Selection Criteria For Studies: Observational and clinical trials investigating the risk of fractures or parathyroidectomy with mineral disturbances.

Predictor: Mineral metabolism variables (phosphorus, calcium, and parathyroid hormone [PTH] levels).

Outcomes: Fractures, need for parathyroidectomy.

Results: 9 studies were identified that assessed fractures (n = 6) or need for parathyroidectomy (n = 3). Data for fractures or parathyroidectomy risk in predialysis patients are absent. Diversity across studies was observed in populations, methods of exposure assessment, adjusted covariates, and reference mineral levels used in risk estimation. A significant fracture risk was observed with increasing PTH levels. However, additional data are required to understand fracture risk with changes in phosphorus or calcium levels. Data supported greater parathyroidectomy risk with increasing PTH, phosphorus, or calcium levels.

Limitations: Clinical and method heterogeneity across studies precluding the quantitative synthesis of data.

Conclusions: Serious limitations were observed in the number, quality, and method rigor of studies. Despite heterogeneity across studies, data suggest a significant parathyroidectomy risk with mineral disturbances and a fracture risk with increasing PTH levels in dialysis patients. Additional high-quality data for risk of fractures or parathyroidectomy with changes in phosphorus, calcium, or PTH levels is required to highlight the importance of managing such common, but subclinical, conditions as mineral metabolism disturbances.