Shift in Calcium From Peripheral Bone to Axial Bone After Tumor Resection in Patients With Tumor-Induced Osteomalacia

Abstract

Context

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. After successful tumor resection, patients can recover from hypophosphatemia quicky. However, data on the changes in bone mineral density (BMD) and microstructure in the short term after surgery remained unclear.

Objective

This work aimed to investigate the postoperative changes in BMD and microstructure both in peripheral and axial bone in TIO patients.

Methods

We evaluated BMD and microarchitecture in 22 TIO patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) and dual-energy x-ray absorptiometry (DXA) before and 3 months after surgery in this retrospective study.

Results

In this study, a total of 22 TIO patients who had recovered serum phosphate levels postoperatively were enrolled. After surgery, areal BMD (aBMD) increased by 21.6% in the femoral neck, by 18.9% in the total hip, and by 29.5% in the lumbar spine. Moreover, TBS increased by 14.1% (all P < .001). In contrast, trabecular or cortical volumetric BMD (vBMD), and microstructure of trabecular bone (trabecular number, separation and bone volume ratio) and cortical bone (cortical thickness and porosity) at the distal radius or tibia were further deteriorated. Correlation analyses found that changes in femoral neck and total hip aBMD were both conversely associated with changes in trabecular vBMD and bone volume ratio, while positively correlated with change in trabecular separation at the distal radius.

Conclusion

Although aBMD and microstructure in the axial bone were improved, vBMD and microstructure in the peripheral bone were further impaired shortly after surgery. Correlation of improvement of aBMD in the total hip and femoral neck with deterioration of vBMD and microstructure at the distal radius indicated a shift in calcium from the peripheral bone to the axial bone in the short term after tumor resection in TIO patients.

Tumor-induced osteomalacia (TIO), the most prevalent form of acquired hypophosphatemic osteomalacia, is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor (1). Patients with TIO suffer from bone pain, muscle weakness, and fractures. Generalized mineralization defects were revealed by previous histological studies in patients with TIO (2). Consistently, areal bone mineral density (aBMD), which is calculated by bone area and bone mineral content measured by dual-energy x-ray absorptiometry (DXA), has been reported to be reduced in patients with TIO (3). In addition, trabecular bone score (TBS), a textural index evaluating trabecular microarchitecture by calculating pixel gray-level variations using DXA images of the lumbar spine, was also reduced in patients with TIO (4). Recently, high-resolution peripheral quantitative computed tomography (HR-pQCT) has been applied to evaluate the bone condition in patients with TIO. Low volumetric BMD (vBMD), impaired microstructure, and reduced bone strength at the distal radius and tibia in patients with TIO has been reported (4–6).

After resection of the causative tumor, serum phosphate and FGF23 levels could quickly return to normal levels (7). Subsequently, bone pain and muscle weakness could be gradually relieved (8). Regarding the recovery of aBMD after tumor resection, one small-sample–sized study with irregular follow-up observed improvement of aBMD in 7 patients with TIO, as well as increased TBS in 3 patients with TIO (3). We also previously reported evident improvement of aBMD in the axial bone and TBS in TIO patients 1 year after surgery, while vBMD and microstructure in the peripheral bone did not show significant change (4). Considering the accumulation of osteoid during the disease duration and rapid recovery of serum phosphate after tumor resection, changes in the bone parameters in the short term after surgery calls our attention. As far as we know, there has not been any study exploring short-term changes in bone parameters after tumor resection in patients with TIO.

The aim of this study was to investigate the changes in BMD and microstructure both in the axial bone and peripheral bone in patients with TIO shortly after tumor resection.

Materials and Methods

Study Population

This study enrolled patients with TIO who visited and underwent tumor excision surgery at Peking Union Medical College Hospital (PUMCH). The inclusion criteria were (1) age 20 years or older, (2) recovery of serum phosphate level after tumor resection or pathological confirmation of phosphaturic mesenchymal tumor, and (3) completion of synchronous DXA and HR-pQCT scans before and 3 months after tumor resection.

This study was approved by the local ethics committee of the Department of Scientific Research at PUMCH, and informed consent was obtained from all participants before entering the study.

Clinical Characteristics

Clinical characteristics, including age, sex, height, weight, body mass index, height loss, disease duration, mobility impairment, and treatment, were obtained from the patients’ clinical records. Height loss was reported by patients as the difference between current height and maximum height. Disease duration was defined as the time interval (months) from onset to the first visit in our hospital.

Biochemical Measurements

Fasting blood samples were collected for following analyses. Serum calcium, phosphate, alkaline phosphatase (ALP) and creatinine were determined by an autoanalyzer (AU5800, Beckman Coulter). Serum parathyroid hormone (PTH) was determined by an auto-analyzer (DXI800, Beckman Coulter). 25-hydroxyvitamin D (25(OH)D) was determined by an automated Roche electrochemiluminescence system (E601, Roche Diagnostics). Serum 1,25-dihydroxy vitamin D (1,25(OH)₂D) levels were measured by radioimmunoassay (DIAsource ImmunoAssays). Urine was analyzed by an autoanalyzer (Beckman Coulter AU2700) to measure urine phosphate for calculation of urine phosphate for 24 hours (24hUP), urine calcium for 24 hours (24hUCa), and urine creatinine levels. TmP/GFR (tubular maximum reabsorption threshold of phosphate per glomerular filtration rate) was estimated using the Walton and Bijvoet nomogram (9). All measurements of the aforementioned biochemical indexes were conducted at the Department of Laboratory Medicine of PUMCH.

Serum intact FGF23 (iFGF23) was measured by iFGF23 enzyme-linked immunosorbent assay Kit (Kainos Laboratories). The detection limit of the assay was 2 pg/mL for iFGF23. Intra-assay and interassay coefficients of variation were 2% to 3% and 2.1% to 3.8%, respectively.

Dual-Energy X-Ray Absorptiometry

aBMD of the lumbar spine (L1-L4 aBMD), total hip and femoral neck was determined by DXA (Prodigy Advance, GE Healthcare), using enCORE software (version 10.50.086, GE Healthcare) for scan acquisition and analysis. L1 to L4 aBMD was calculated as the mean value of the L1 to L4 measurements. The right hip was scanned unless there was a fracture or implant, in which case the left hip was scanned. Coefficient of variation (CV) of aBMD measurements was 0.94% for the lumbar spine, 0.74% for the total hip, and 1.75% for the femoral neck at our center.

Trabecular Bone Score

TBS was extracted from the DXA image using TBS iNsight software (version 2.1, Medimaps). The spine TBS was calculated as the mean value of the L1 to L4 measurements (10), and the region of interest for calculating TBS was the same as the region of interest for calculating L1 to L4 aBMD. The CV for TBS at our center was 1.14%.

High-resolution Peripheral Quantitative Computed Tomography

Scans were performed with an HR-pQCT scanner (XtremeCT II, Scanco Medical AG) with an isotropic voxel size of 61 μm on patients with TIO. The nondominant arm and corresponding leg of the patients were scanned. Reference lines were set on the distal endplate of the scanned limbs of the participants. A total of 168 CT slices were acquired from 9.0 and 22.0 mm proximal to the reference line for the distal radius and tibia, respectively. All image analyses were performed according to standard in vivo acquisition protocols provided by the manufacturers. The periosteal surface of the bone was identified automatically and corrected manually as necessary. An Image Processing Language (version 5.42, Scanco Medical) algorithm was applied to identify the endosteal surface and segment the cortical and trabecular compartments. Trabecular vBMD (Tb.vBMD), cortical vBMD (Ct.vBMD), and cross-sectional area of trabecular bone (Tb.Ar) and cortical bone (Ct.Ar) were directly measured after successful segmentation of different compartments. Trabecular bone volume ratio (Tb.BV/TV), number (Tb.N), thickness (Tb.Th) and separation (Tb.Sp), and cortical thickness (Ct.Th) and porosity (Ct.Po) were also calculated directly. μFinite element analysis (μFEA) was performed to obtain information on estimated bone strength using the Scanco Finite Element software (vision 1.13; Scanco Medical). CV was 0.4% to 0.8% for the vBMD parameters, 0.2% to 1.2% for the areal parameters, 0.6% to 3.9% for the trabecular microstructural parameters, 0.9% to 1.1% for Ct.Th, and 14.1% to 19.2% for Ct.Po at our center.

Statistical Analyses

Continuous variables are presented as mean ± SD or median (interquartile range) as appropriate, whereas categorical variables are presented as frequency (percentage). Mean percentage changes in bone parameters after surgery are presented as mean ± SEM. Differences between bone parameters before surgery and after surgery were analyzed by paired T test for normally distributed continuous data, and Wilcoxon signed rank test for nonparametric continuous data. Bivariate correlation was assessed by the Pearson or Spearman correlation test. P less than .05 was considered statistically significant in 2-tailed tests. All statistical analyses were performed using IBM SPSS Statistical Software, version 23 (SPSS Inc).

Results

Baseline Characteristics of Enrolled Patients With Tumor-Induced Osteomalacia

The baseline characteristics of 22 patients with TIO are shown in Table 1. This study included 15 male and 7 female patients aged 40.5 ± 11.9 years with a disease duration of 49.3 ± 24.6 months. The height loss found in our patients was 4.5 cm (range, 2.0-8.0 cm). Six patients relied on a wheelchair, 7 patients needed a crutch, and the remaining 9 patients were able to walk without a crutch but needed aids in certain cases, such as climbing stairs. Seven patients (31.8%) were supplemented with phosphate, and 11 patients (50%) were supplemented with calcitriol for at least 6 months before visiting PUMCH. Laboratory measurements confirmed hypophosphatemia in TIO patients. Low Tmp/GFR, high iFGF23 levels, and 24hUP suggested that renal phosphate-wasting was responsible for the hypophosphatemia in TIO patients. We also found elevated serum ALP levels, high β-CTx and P1NP levels, and low 1,25(OH)₂D and 25OHD levels in TIO patients (see Table 1).

Recovery of Serum Phosphate and Improvement of Alkaline Phosphatase After Tumor Resection

At the time of the 3-month follow-up, all patients recovered from hypophosphatemia. The serum phosphate levels in them after surgery were significantly increased (0.48 ± 0.10 vs 1.45 ± 0.27 mmol/L; P < .001), ranging from 0.82 mmol/L to 1.90 mmol/L. Moreover, serum ALP decreased greatly (317 ± 133 vs 218 ± 115 U/L; P < .001), while β-CTx significantly increased (0.841 ± 0.456 vs 2.181 ± 1.267 ng/mL; P < .001). After tumor resection, PTH levels also tended to increase (57.2 [45.0-81.8] vs 72.0 [46.0-93.9] pg/mL; P = .122). However, serum iFGF23 levels were not measured 3 months after surgery. During the 3 months, 11 patients received supplementation of calcium and calcitriol, 5 patients only received calcitriol, and the remaining 6 patients were not treated.

Changes in Dual-Energy X-Ray Absorptiometry Parameters in Axial Bone Shortly After Tumor Resection

To explore the changes in aBMD in the axial bone and TBS of the lumbar spine, we compared the aBMD and TBS before and 3 months after surgery in 22 TIO patients (Table 2). One patient had invalid data of hip aBMD after acetabulectomy because the operating side was scanned by mistake. As shown in Fig. 1 and Fig. 2, 3 months after surgery, aBMD increased by 21.6% in the femoral neck (0.651 ± 0.148 vs 0.767 ± 0.106 g/cm²; P < .001), and by 18.9% in the total hip (0.658 ± 0.165 vs 0.779 ± 0.122 g/cm²; P < .001). In addition, lumbar spine aBMD increased by 29.5% (0.872 ± 0.220 vs 1.092 ± 0.238 g/cm²; P < .001). Meanwhile, TBS also showed statistically significant improvement with an increase of 14.1% (1.122 ± 0.129 vs 1.278 ± 0.124; P < .001) postoperatively.

Changes in High-Resolution Peripheral Quantitative Computed Tomography Parameters in Peripheral Bone Shortly After Tumor Resection

We also compared the HR-pQCT parameters before and 3 months after tumor resection to explore the changes in vBMD and microstructure in the peripheral bone (Table 3). At the distal radius, Ct.Ar was slightly decreased 3 months after surgery (68.7 ± 16.9 vs 67.0 ± 15.6 mm²; P = .045), while Tb.Ar was unchanged. Although Ct.vBMD was maintained, Tb.vBMD was significantly decreased (130.5 ± 59.2 vs 118.9 ± 56.9 mgHA/cm³; P = .002). Consistently, both Tb.BV/TV (19.8 ± 8.0 vs 18.2 ± 7.4%; P = .007) and Tb.N (1.182 ± 0.384 vs 1.099 ± 0.382 1/mm; P = .025) were significantly decreased, with increased Tb.Sp (0.774 [0.638-1.063] vs 0.880 [0.636-1.185] mm; P = .011). Ct.Th was also decreased (1.115 ± 0.256 vs 1.092 ± 0.236 mm; P = .045), but Ct.Po did not change. At the tibia, both Tb.Ar and Ct.Ar were unchanged. Ct.vBMD (832.1 ± 79.7 vs 819.6 ± 60.1 mgHA/cm³; P = .046) was decreased with increased Ct.Po (2.7 ± 1.4 vs 3.5 ± 1.5%; P = .019). Although the decline of Tb.vBMD was not statistically significant, Tb.BV/TV decreased significantly (20.7 [14.3- 24.8] vs 16.7 [13.7-21.2]%; P = .006), with decreased Tb.N (1.015 ± 0.271 vs 0.960 ± 0.298 1/mm; P = .013) and increased Tb.Sp (0.916 [0.792-1.303] vs 1.003 [0.829-1.254] mm; P = .024). Estimated bone strength both at the distal radius and tibia did not change significantly. Mean percentage changes in HR-pQCT parameters after tumor resection are presented in Fig. 3.

Correlation of Improvement of Dual-Energy X-Ray Absorptiometry Parameters in Axial Bone With Deterioration of High-Resolution Peripheral Quantitative Computed Tomography Parameters in Peripheral Bone

Next, we tried to explore the correlation of changes in aBMD and TBS derived from DXA with changes in vBMD and microstructure evaluated by HR-pQCT. We found that the change in femoral neck aBMD was conversely associated with changes in Tb.vBMD (r = −0.622; P = .003) and Tb.BV/TV (r = −0.516; P = .017), while almost correlated positively with change in Tb.Sp (r = 0.413; P = .063) at the distal radius (Fig. 4A-4C) (n = 21). Similar correlations of change in total hip aBMD with changes in Tb.vBMD, Tb.BV/TV, and Tb.Sp at the distal radius were also observed (Fig. 4D-4F) (n = 21). However, vBMD and microstructural parameters at the distal tibia did not significantly correlate with DXA parameters. In addition, we did not observe a statistically significant correlation between L1 to L4 aBMD and HR-pQCT parameters.

Both the improvement of DXA parameters in the axial bone and deterioration of HR-pQCT parameters in the peripheral bone were not associated with disease duration.

Discussion

In this study, we first explored the changes both in the axial bone and peripheral bone 3 months after successful tumor resection with recovery of serum phosphate levels in TIO patients. We observed unexpected opposite changes in bone parameters in the axial bone and peripheral bone, as aBMD and TBS in axial bone were significantly improved, while partial parameters reflecting vBMD and microstructure in peripheral bone were strikingly declined. Improvement of aBMD in total hip and femoral neck showed significant correlation with deterioration of vBMD and microstructure at the distal radius.

After the recovery of phosphate levels, elevation of BMD was expected after tumor resection due to the restored mineralization of the huge accumulated osteoid during the disease duration. Actually, we have previously reported obvious improvement of aBMD in the axial bone and TBS in 15 TIO patients 1 year after surgery (4). A similar finding has been reported in a study of 7 patients with data of aBMD and 3 patients with data of TBS after irregular follow-up (3). In this study, it was surprising to find that, even only 3 months after surgery, significant improvement of aBMD in the axial bone could be observed. At the same time, TBS increased significantly, suggesting improved microstructure of lumbar spine. These results uncovered the rapid initiation of regain of both aBMD and microstructure due to the remineralization of osteoid in the axial bone in TIO patients after successful tumor resection.

Similarly, vBMD and microstructure in the peripheral bone were also expected to be ameliorated after tumor resection. However, in our previous study, we did not observe obvious improvement of vBMD and microstructure in the peripheral bone 1 year after surgery in 15 TIO patients (4). Conversely, Ct.Po at the tibia even became larger. We therefore wondered what happened to the peripheral bone within 1 year after tumor resection. In this study, we were surprised to observe that both vBMD and microstructure in the peripheral bone further deteriorated 3 months after surgery. This finding was not consistent with our expectation, since both aBMD and microstructure in the axial bone were improved. Actually, the deterioration of peripheral bone observed after surgery certainly cannot be due to an age-related deterioration, as the annual rate of change in HR-pQCT parameters revealed by a previous population-based HR-pQCT study was much lower than the changes in HR-pQCT parameters found in TIO patients 3 months after surgery (11). Although vBMD and microstructure declined in the peripheral bone after surgery, estimated bone strength by FEA did not change significantly. Compensatory bone strength in the condition of impaired bone microstructure could be explained by structural adaptation with larger bone area in child-onset X-linked hypophosphatemia (12). However, all TIO patients enrolled in this study were adult-onset, and enlarged bone area was not found, suggesting another potential compensatory mechanism.

To explore the possible reason for the further deterioration of vBMD and microstructure at the distal radius and tibia, considering the opposite trend of changes in the axial and peripheral bone, we then analyzed the correlation of changes in aBMD and TBS of the axial bone with changes in vBMD and microstructure in the peripheral bone. Both changes in femoral neck aBMD and total hip aBMD were negatively correlated with change in Tb.vBMD at the distal radius, suggesting that the greater decrease of Tb.vBMD at the distal radius was associated with greater increase of aBMD in the femoral neck and total hip. In addition, both changes in femoral neck aBMD and total hip aBMD tended to positively correlate with change in Tb.Sp at the distal radius, suggesting that the greater increase of Tb.Sp at the distal radius was associated with greater increase of aBMD of the femoral neck and total hip. All of the findings revealed that the larger extent of deterioration that occurs at the distal radius, the larger extent of improvement that happens to the total hip and femoral neck. A possible explanation could be the improved mobility and subsequent reduced mechanical stimulation of upper limbs due to walking without a crutch after successful surgery. Based on the correlations of changes in aBMD in the axial bone (total hip and femoral neck) and changes in vBMD and microstructure at the distal radius, we hypothesized that a shift in calcium from peripheral bone to axial bone existed after tumor resection, especially trabecular bone, giving priority to recovery of axial bone. Nevertheless, we did not observe a significant correlation of changes in aBMD and microstructure of the lumbar spine with changes in vBMD and microstructure in peripheral bone. QCT is expected to be applied in a future study to further explore the correlation. In addition, different from the findings at the distal radius, change in parameters at the distal tibia did not shown a correlation with changes in axial bone parameters. The absent correlation between tibia and axial bone may be due to the similar characteristics between tibia and axial bone as load-bearing bone. The speculation proposed here needs more studies to confirm in the future.

From the perspective of biochemical indices, we found the postoperative PTH levels in TIO patients tended to increase compared with that before surgery. This finding is consistent with the exacerbation of secondary hyperparathyroidism in TIO patients within a few days after surgery reported previously (13). Based on previous in vivo and in vitro studies confirming that FGF23 can inhibit the expression and secretion of PTH (14), we speculate that the sharp decrease in FGF23 after tumor resection relieved the inhibition of PTH by FGF23, leading to an increase in postoperative PTH levels. PTH levels during postoperative hospitalization had been monitored in a small number of patients in our center. The data suggest that PTH levels significantly increase within a few days after surgery (data not published) and then gradually decline to normal range. In this study, postoperative PTH levels were collected at the 3-month follow-up after surgery, rather than within a few days after surgery. This might explain the nonsignificant increase in PTH levels after surgery. Regarding the effect of PTH on bones, DXA and HR-pQCT studies in patients with hyperparathyroidism have suggested that excessive endogenous PTH is more catabolic in non–weight-bearing bone than in weight-bearing bone (15, 16). Therefore, the catabolic effect of high PTH levels on the non–weight-bearing distal radius of TIO patients may be greater than the effect of osteoid remineralization after surgery; the final manifestation then is the further deterioration of BMD and bone microstructure. By contrast, lumbar spine and hip mainly show the effect of osteoid remineralization after surgery, and the final result is the improvement of BMD and bone microstructure. Further deterioration at the distal tibia after tumor resection suggests that the catabolic effect of PTH on the distal tibia is stronger than osteoid remineralization. Although both are weight-bearing bone, the distal tibia and lumbar spine (or hip) showed opposite changes after surgery. A possible explanation is that the distal tibia is mainly composed of a cortical component, and PTH has a stronger catabolic effect on cortical bone than on trabecular bone (17).

However, whether the calcium shift from peripheral bone to hip and femoral neck shortly after tumor resection found in this study will be continuous or interrupted, or even reversed in the long term, remains unknown. Here, we did not clarify this issue since the number of patients who completed 1-year follow-up among these TIO patients is too small to draw a reliable result. Although most HR-pQCT parameters 1 year after surgery were comparable to those before surgery in 15 TIO patients in our previous study (4), suggesting that deterioration of microstructure in the peripheral bone shortly after surgery might be reversed within 1 year after surgery, different individuals enrolled in these 2 studies hinder us from linking the findings together to obtain a reliable conclusion. Thus, larger sample-sized studies with longer and more regular follow-up are needed to explore synchronous changes in BMD and microstructure in the axial bone and peripheral bone after surgery in TIO patients.

Our study has some limitations. First, due to the rarity of TIO and irregular follow-up, a relatively small number of patients were evaluated in this study. Further studies are needed to confirm our findings. Second, we speculated the shift in calcium from peripheral bone to axial bone after surgery in TIO patients based on the correlation of changes in vBMD and microstructure at the distal radius with changes in aBMD of the total hip and femoral neck, while the potential mechanism was unclear. Third, as mentioned earlier, also because of the irregular follow-up, changes in BMD and microstructure were not observed continuously with a longer follow-up.

In conclusion, we first revealed that recovery of aBMD and microstructure of axial bone was initiated quickly and reached to a large extent even only 3 months after successful tumor resection. However, vBMD and microstructure in the peripheral bone were further impaired after surgery. Correlation of improvement of femoral neck aBMD and total hip aBMD with deterioration of vBMD and microstructure at the distal radius indicated a shift in calcium from the peripheral bone to the axial bone after tumor resection in TIO patients.

Acknowledgments

We thank our patients for their participation in this study.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81970757, No. 81900798, and No. 82100942), Chinese Academy of Medical Sciences Innovation Fund for Medical Science (No. 2021-I2M-1-002 and No. 2020-I2M-C&T-B-016), National Key Research and Development Program of China (No. 2021YFC2501700 and No. 2018YFA0800801), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-A-202).

Disclosures

The authors have nothing to disclose.

Data Availability

Some or all data sets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

References

Abbreviations

 
• 1,25(OH)₂D

  1,25-dihydroxyvitamin D

 
• 24hUCa

  urine calcium for 24 hours

 
• 24hUP

  urine phosphate for 24 hours

 
• 25(OH)D

  25-hydroxyvitamin D

 
• aBMD

  areal bone mineral density

 
• ALP

  alkaline phosphatase

 
• BMD

  bone mineral density

 
• Ct.Ar

  cortical bone area

 
• Ct.Pm

  cortical perimeter

 
• Ct.Po

  cortical porosity

 
• Ct.Th

  cortical thickness

 
• Ct.vBMD

  cortical volumetric BMD

 
• CV

  coefficient of variation

 
• DXA

  dual-energy x-ray absorptiometry

 
• FEA

  finite element analysis

 
• FGF23

  fibroblast growth factor 23

 
• HR-pQCT

  high-resolution peripheral quantitative computed tomography

 
• iFGF23

  intact fibroblast growth factor 23

 
• PTH

  parathyroid hormone

 
• PUMCH

  Peking Union Medical College Hospital

 
• Tb.Ar

  trabecular bone area

 
• Tb.BV/TV

  trabecular bone volume ratio

 
• Tb.N

  trabecular number

 
• TBS

  trabecular bone score

 
• Tb.Sp

  trabecular separation

 
• Tb.Th

  trabecular thickness

 
• Tb.vBMD

  trabecular volumetric BMD

 
• TIO

  tumor-induced osteomalacia

 
• TmP/GFR

  tubular maximum reabsorption threshold of phosphate per glomerular filtration rate