The existing body of evidence suggests that cinacalcet isan effective drug for secondary hyperparathyroidism(SHPT) control in patients undergoing maintenance dialy-sis (CKD-5D) [1–10]. Indeed, available evidence suggeststhat by modulating the parathyroid calcium-sensing re-ceptor affinity to serum calcium, cinacalcet lowers by40–50% (250–350 pg/mL) serum parathyroid hormone(PTH) (Table 1). A consensual reduction in calcium [∼0.5–0.8 mg/dL (0.125–0.200 mmol/L); 5–8%] (Table 1) is alsoreported and expected due to the calcium-PTH set pointchange induced by this drug [11, 12]. However, some,albeit not all, reports (Table 1) have described a consen-sual reduction in serum phosphorus, which is more com-plicated to explain and often confounded by theconcomitant use of other agents such as vitamin D andphosphate binders that significantly affect phosphorousmetabolism [13, 14].Serum phosphorous represents a minimal part (∼1%) ofthe total body pool and is regulated by the net amount ab-sorbed in the intestine, the quota excreted by the kidneysand the net amount exchanged by the bones in the timeunit [13]. Notably, serum phosphorous does not alwaysclosely mirror the total body pool and phosphorousbalance in CKD, since different hormones regulate renaltubular (i.e. FGF-23, FGF-7, PTH) and bone (i.e. PTH) phos-phate handling to avoid excessive fluctuations of serumphosphorous concentration [13–15]. However, in CKD-5Dpatients the amount excreted by the kidneys is minimal ifnot absent. Hence, the reported tendency of cinacalcet toreduce serum phosphorous cannot be explained bya ‘renalcompensation’, but rather by the PTH effect on bones.We read with interest the manuscript by Zitt et al. [16].The aim of their study was to elucidate the mechanismsby which cinacalcet may lower serum phosphorous. Inthis observational study (ECHO study) [16], the authorsreport an overall tendency towards phosphate reduction(median change −9.1%, interquartile range: −25% to+10%), after 12 months of cinacalcet therapy [16]. Each10% serum PTH reduction correlates with a 3% decreasein serum phosphorous in the ECHO study cohort [16].However, at least 25% of the study population experi-enced an increase in serum phosphorous (median change−9.1%, interquartile range: −25% to +10%) [16] in spiteof the treatment with cinacalcet. The use of othercompounds such as vitamin D or phosphate binders aswell as the lack of diet control might explain why not allpatients treated with cinacalcet exhibit a consensualserum phosphorous reduction, but authors documentthat among 45% of patients in which serum phosphorousdecreases [defined as a change of at least 0.1 mg/dL(0.0323 mmol/L)], the use of concomitant medicationscannot explain this trend (vitamin D either increased orremained unchanged and phosphate binders were eitherreduced or left unchanged during follow-up). Finally, thelack of association between cinacalcet dose and serumphosphorous corroborates the hypothesis that bonemetabolism may playa role at least in some patients whoexperience a phosphate reduction while on cinacalcettreatment, similarly to what was seen after surgical para-thyroidectomy [17]. The role of bone metabolism couldalso be hypothesized by the multivariable-adjusted andsensitivity analyses. Adjustment for factors associatedwith serum phosphorus in CKD-5D patients documentsthat baseline serum phosphorous, dialysis vintage andPTH change from baseline to month 12 are the major de-terminants of phosphorus reduction at follow-up [16].However, sensitivity analyses document that a significantserum phosphate reduction is noted in all but the lowestbaseline PTH quartile and PTH change at Month 12 [17],suggesting that the quota of phosphate removed fromthe bone is relevant among subjects with severe SHPT oramong patients with parathyroid gland tissue still respon-sive to a calcimimetic drug (i.e. greater PTH reduction).The findings reported by Zitt et al. are consistent withprevious reports (Table 1 ). Though all studies recruited sub-jects with on average a poorly controlled PTH (in the rangeof 500–700 pg/mL), not all patients experienced a de-crease in serum phosphate. However, no study has con-trolled the use of phosphate binders and vitamin Dchanges during follow-up. In this regard, Zitt et al. furtherexpand the body of knowledge showing this trend amongpatients who did not decrease vitamin D or increase phos-phate binder usage at follow-up. Nonetheless, the obser-vational nature and the potential of imbalance amongdifferent groups (data not reported) and the lack of phos-phate intake evaluation at baseline and during follow-up,caution against definitive conclusions about the role ofPTH and the generalizability of the authors’ results.