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Keywords:

  • osteocyte;
  • mineralization;
  • PTH;
  • secondary hyperparathyroidism;
  • parathyroidectomy;
  • chronic kidney disease

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

In order to gain insight into the mechanisms underlying the dynamic changes in bone metabolism and bone quality after parathyroidectomy (PTX) in secondary hyperparathyroid patients with high levels of parathyroid hormone (PTH), we performed bone histomorphometric analysis with tetracycline labeling in iliac bone biopsy specimens taken before and after PTX, with special attention paid to osteocytes. At 2 to 4 weeks after PTX, PTH concentrations decreased markedly with evident reductions in bone turnover markers. Histomorphometry revealed that at 2 to 4 weeks following PTX, the osteoclast surface decreased to nearly 0%, with a substantial increase in osteoid volume and a reduction in fibrosis volume. Labeling with tetracycline was observed not only at the mineralization front on the bone surface but also around the osteocyte lacunar walls and canaliculi within both the basic multicellular units (BMUs) and bone structural units (BSUs), suggesting that mineralization was taking place along the lacunocanalicular system after PTX. The tetracycline-labeled area was much greater in the BSUs than in the BMUs and at the mineralization front, and the tetracycline labeling in the BSUs was markedly increased after PTX compared with that in the low- and high-PTH control groups without PTX. The osteocyte number was decreased significantly after PTX, concomitant with an increase in the number of empty lacunae and a reduction of lacunar volume. Thus the increased osteocyte death and mineralization around the lacunocanalicular system in association with a rapid decline in PTH may underlie the changes in bone metabolism and quality that occur following PTX. © 2010 American Society for Bone and Mineral Research.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

Chronic kidney disease (CKD) is recognized as a multi-organ-system disorder involving the kidney, skeleton, parathyroid glands, and cardiovascular system, collectively termed CKD–mineral bone disorder (MBD).1 The increasing incidence of CKD has a significant impact on the mortality rate worldwide.

As renal function declines, hyperphosphatemia, calcitriol deficiency, and hypocalcemia contribute to the development of secondary hyperparathyroidism and skeletal complications classically called renal osteodystrophy (ROD).1 The pathology of ROD is diverse, ranging from high-turnover bone disease, termed osteitis fibrosa, which takes place in the presence of sustained high parathyroid hormone (PTH) levels, to low-turnover osteomalacia and adynamic bone disease (ABD) on the other end of the spectrum and their mixed forms.2, 3 Active vitamin D drugs are frequently administered to patients with secondary hyperparathyroidism to suppress PTH levels; however, the oversuppression of PTH results in the development of ABD. Whether in the high- or low-PTH milieu, a net negative balance between bone resorption and formation results in osteopenia or osteoporosis,4 and a higher rate of fracture has been observed in patients with end-stage renal disease.5

Despite medical treatment, parathyroidectomy (PTX) is required in many patients with secondary hyperparathyroidism, and the impact of PTX on skeletal health and fracture risk has not been adequately clarified. Abdelhadi and colleagues reported that bone mineral density (BMD) not only in patients with primary hyperparathyroidism but also in patients with secondary hyperparathyroidism associated with hemodialysis was reduced at baseline and increased following PTX.6 Further, Rudser and colleagues have reported recently that PTX was associated with an approximately 30% lower risk for fracture among hemodialysis patients.7 The mechanism for the reduced fracture risk after PTX, however, is not known.

Bone strength is determined by both the quantity of bone and the material and structural properties of bone, to the latter of which ostecytes are believed to contribute significantly.8 Osteocytes are known to account for over 90% of all bone cells and to regulate bone remodeling so as to maintain bone quality and serve as the mechanosensory cells of bone.9 Therefore, we hypothesized that changes in osteocyte function might underlie bone stability after PTX, thus accounting for the reduced fracture risk. In an attempt to address this question, we examined the number and surrounding mineralization of ostecytes by bone histomorphometry using iliac bone biopsy specimens obtained before and after PTX in patients with secondary hyperparathyroidism.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

Patients

Eighteen patients with secondary hyperparathyroidism undergoing hemodialysis, including 11 males and 7 females, were enrolled in the study; they were aged 58.8 ± 9.5 (39 to 74) years and had a duration of hemodialysis 13.6 ± 7.0 (1 to 25) years. The underlying renal diseases included chronic glomerulonephritis in 13 patients, polycystic kidney disease in 1 patient, hypertension in 1 patient, and unknown in 3 patients. The body mass index (BMI) of the patients was 21.2 ± 2.4 (17.0 to 25.8) kg/m2. All the patients underwent PTX with immediate autotransplantation. Transiliac bone biopsy specimens were obtained before and at 2 to 4 weeks after PTX to study the effects of the abrupt decline in serum PTH and suppression of bone remodeling on osteocyte number and mineralization around lacunar walls in cancellous bone. The use of vitamin D analogues was discontinued for at least 2 months prior to PTX to avoid surgical complications caused by the prolonged elevation of serum calcium levels and calcium × phosphorus products.

In addition to the 18 subjects just mentioned, 7 hemodialysis patients (5 males and 2 females) aged 64.9 ± 9.3 (56 to 81) years and with a duration of hemodialysis of 11.6 ± 9.8 (2 to 31) years who exhibited persistently low serum PTH levels [intact PTH levels of 35.8 ± 58.3 (18 to 233) pg/mL] without prior PTX were recruited as control subjects with sustained low PTH (low-PTH control). All these patients were diagnosed as having adynamic bone disease (ABD). In addition, 7 patients with secondary hyperparathyroidism aged 58.4 ± 8.6 (44 to 70) years and with a duration of hemodialysis of 13.6 ± 4.8 (7 to 20) years also were recruited as control subjects with high PTH and without PTX (high-PTH control). Among these, 4 patients were diagnosed as having osteitis fibrosa, with serum intact PTH levels of 753.3 ± 171.6 (530 to 1110) pg/mL, and 3 patients were diagnosed as having mild bone disease, with serum intact PTH levels of 640.0 ± 246.7 (330 to 880) pg/mL.

None of the patients suffered from diabetes mellitus or liver dysfunction. The calcium concentration in the dialysis water was 2.5 mEq/L, and the serum calcium levels were relatively stable, with calcium × phosphorus product values of under 70 mg2/dL2 at the time of PTX in the study group (n = 18) and at the time of bone biopsies in the low-PTH (n = 7) and the high-PTH control groups (n = 7). Informed consent was obtained from all patients after they were provided with a detailed explanation of both the risks and possible outcomes of bone biopsies and PTX. The Institutional Review Board of Towa Hospital and its affiliated hospitals approved the study protocol.

Parathyroidectomy (PTX)

The 18 patients in the study group underwent PTX with immediate autotransplantation of 150 mg of diffuse hyperplastic parathyroid tissue into the adipose tissue of the abdominal wall. This autotransplantation was performed to avoid the long-term low bone turnover state after PTX. Serum intact PTH values fell to below 30 pg/mL by 1 week postoperatively in all but two patients (only three parathyroid glands were removed in one patient, and in the other, four glands were removed with one additional gland left unremoved, and 50 mg instead of 150 mg of the parathyroid tissue was autotransplanted in these two patients).

Serum biochemical analysis

Serum biochemistry was analyzed before and at the time of the second bone biopsy performed 2 to 4 weeks after PTX. Serum intact PTH was measured by an immunoradiometric assay (Allegro Intact PTH, Nichols Institute Diagnostics, San Juan Capistrano, CA, USA) or an electrochemiluminescence immunoassay (Elecsys PTH, Roche Diagnostics GmbH, Mannheim, Germany), and deoxypyridinoline (DPD) and tartrate-resistant acid phosphatase (TRACP) were measured as described previously.10, 11

Bone histomorphometry

The first bone biopsy specimen was obtained using a trephine (8 mm in diameter) from the left iliac crest just prior to PTX, and the second specimen was obtained from the right iliac crest after the surgery. Of the 18 patients in the study group, 17 underwent bone biopsies both before and at 2 to 4 (3.6 ± 0.7) weeks after PTX, and the remaining 1 patient underwent a single bone biopsy at 4 weeks after PTX. The biopsy specimens were fixed in ethanol, stained by the Villanueva method, and embedded in methyl methacrylate without decalcification.

Prior to the post-PTX biopsy, 16 of the 18 patients underwent double tetracycline labeling by oral administration of tetracycline hydrochloride according to a 3-10-3-4 (or 5) schedule, that is, administration on 3 consecutive days with a 10-day interval, and bone biopsy was performed 4 or 5 days after the last administration, except for 2 patients, whose bone biopsy was performed at 2 weeks after PTX according to a 2-8-1-2 labeling schedule.12 One of the authors (AI) analyzed the histomorphometric parameters in 25 sections of each specimen. The results of bone histomorphometric analysis were expressed according to the methods of Parfitt and colleagues,13 except for the osteocyte parameters. The parameters related to osteocytes were as follows: number of osteocytes (N.Ot) and number of empty lacunae (N.Empty.Lc). Osteocytes were readily identified in the bone matrix, and empty lacunae were defined as lacunae without any visible cell remnants inside.14 Secondary parameters, including bone volume (BV)–referent N.Ot (N.Ot/BV), N.Ot in basic multicellular unit (BMU) (N.Ot in BMU/BV), N.Ot in bone structural unit (BSU) (N.Ot in BSU/BV), and N.Empty.Lc (N.Empty.Lc/BV), also were calculated.

Bone areas labeled by tetracycline were divided by the sum of the intervals (in days) from the date of the first administration through the date of bone bioposy.12 Then the BV-referent tetracycline-labeled area was calculated separately at the mineralization front (MF-TC.V/BV/day; %/day) and around the osteocyte lacunar walls and canaliculi in the BMU (Ot-TC.V in BMU/BV/day; %/day) and the BSU (Ot-TC.V in BSU/BV/day; %/day).

Statistical analysis

Data are expressed as mean ± SD. The differences in the parameters before and after PTX were evaluated by Wilcoxon's signed-rank test. The differences in the parameters between the PTX group and high-PTH control or low-PTH control group were assessed by unpaired Student's t test. P values of less than .05 were considered to indicate statistical significance.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

Serum biochemical analysis

As shown in Table 1, serum intact PTH levels decreased markedly from 1256.7 ± 448.2 to 30.3 ± 61.6 pg/mL (p < .001) at 2 to 4 weeks after PTX in patients with secondary hyperparathyroidism. In fact, serum intact PTH fell to below 30 pg/mL by 1 week postoperatively in all but 2 subjects, in whom the reduction in serum PTH was incomplete (76 and 264 pg/mL) at the time of bone biopsy performed 4 weeks after PTX. Serum calcium concentrations showed a nonsignificant trend for an increase in part because the patients were on oral alfacalcidol (1α-hydroxyvitamin D3) with large doses of intravenous calcium gluconate or oral calcium carbonate supplementation postoperatively. Serum phosphate levels decreased significantly from 5.3 ± 1.2 to 2.9 ± 1.6 mg/dL (p = .001) after PTX (Table 1).

Table 1. Serum Biochemistry Before and After PTX in Patients With Secondary Hyperparathyroidism
VariablesNormal valuesBefore PTXAfter PTXp
  1. Note: Serum biochemical analysis was performed before and at 2 to 4 weeks after PTX. All values are expressed as means ± SD (n = 18).

Intact PTH (pg/mL)10–651256.7 ± 448.230.3 ± 61.6<.001
TRACP (U/L)5.5–17.222.3 ± 8.47.4 ± 3.0<.001
DPD (pmol/mL)45.1 ± 40.29.3 ± 4.1<.001
ALP (U/L)85–255683.6 ± 462.1966.8 ± 510.4<.001
Ca (mg/dL)8.4–10.49.9 ± 0.810.5 ± 1.80.332
P (mg/dL)2.5–4.55.3 ± 1.22.9 ± 1.60.001

With respect to bone turnover markers, the serum levels of TRACP decreased significantly from 22.3 ± 8.4 to 7.4 ± 3.0 U/L (p < .001) along with a substantial decrease in DPD from 45.1 ± 40.2 to 9.3 ± 4.1 pmol/mL (p < .001) at 2 to 4 weeks after PTX. Serum levels of alkaline phosphatase (ALP) increased significantly from 683.6 ± 462.1 to 966.8 ± 510.4 U/L (p < .001) after the surgery (Table 1).

Bone remodeling parameters

Bone histomorphometry revealed that the osteoclast surface (Oc.S/BS) decreased markedly from 4.4 ± 3.6 to 0.1 ± 0.5% (p < .001), along with a reduction in the eroded surface (ES/BS) from 27.7 ± 10.6 to 3.1 ± 2.7% (p < .001) after PTX (Table 2). Osteoid volume (OV/BV) increased substantially from 11.3 ± 8.3 to 19.1 ± 8.9% (p = .002), along with increases in osteoid surface (OS/BS) from 54.9 ± 18.0 to 82.5 ±18.2% (p = .001) and osteoid thickness (O.Th) from 13.9 ± 7.3 to 19.6 ± 8.6 µm (p < .001) in cancellous bone after PTX. Although we previously reported that the osteoblast surface (Ob.S/BS) increased at 1 week after PTX,11, 12 no significant increase in Ob.S/BS was observed at 2 to 4 weeks after the surgery. Fibrosis volume (Fb.V/TV) decreased significantly from 4.6 ± 3.8 to 0.6 ± 1.6% (p < .001) following PTX (Table 2).

Table 2. Static Histomorphometric Parameters Before and After PTX
VariablesBefore PTXAfter PTXp
  1. Note: Iliac bone biopsy was performed before and at 2 to 4 weeks after PTX. Osteoclast surface (Oc.S), eroded surface (ES), osteoblast surface (Ob.S), and osteoid surface (OS) were corrected for bone surface (BS). Fb.V = fibrosis volume; O.Th = osteoid thickness All values are expressed as means ± SD (n = 17).

Oc.S/BS (%)4.4 ± 3.60.1 ± 0.5<.001
ES/BS (%)27.7 ± 10.63.1 ± 2.7<.001
Fb.V/TV (%)4.6 ± 3.80.6 ± 1.6<.001
Ob.S/BS (%)22.3 ± 10.522.1 ± 22.70.653
OV/BV (%)11.3 ± 8.319.1 ± 8.90.002
OS/BS (%)54.9 ± 18.082.5 ± 18.20.001
O.Th (µm)13.9 ± 7.319.6 ± 8.6<.001

Parameters related to osteocytes

As shown in Table 3, in all the cancellous bone areas, including the BMU and BSU, N.Ot/BV decreased significantly from 227.6 ± 63.8 to 188.1 ± 45.8 N/mm2 (p = .002) following PTX. When the osteocytes were counted separately in the BMU and BSU, they decreased from 369.9 ± 101.0 to 258.8 ± 82.8 N/mm2 (p < .001) and from 174.3 ± 40.2 to 149.0 ± 46.9 N/mm2 (p = .025), respectively, after PTX. Conversely, N.Empty.Lc/BV increased significantly from 13.6 ± 9.6 to 39.9 ± 16.1 N/mm2 (p < .001) in all the cancellous bone areas after PTX (Fig. 1, Table 3). The osteocyte lacunar volume also was reduced following PTX (Fig. 2, Table 3).

Table 3. Decreased Osteocyte Numbers After PTX
VariablesBefore PTXAfter PTXp
  1. Note: Iliac bone biopsy was performed before and at 2 to 4 weeks after PTX. Osteocyte number (N.Ot), osteocyte number in BMU and in BSU, number of empty lacunae (N.Empty.Lc), and total lacunar volume (Tt.Lc.V) were corrected for bone volume (BV). All values are expressed as means ± SD (n = 17).

N.Ot/BV (N/mm2)227.6 ± 63.8188.1 ± 45.80.002
N.Ot in BMU/BV (N/mm2)369.9 ± 101.0258.8 ± 82.8<.001
N.Ot in BSU/BV (N/mm2)174.3 ± 40.2149.0 ± 46.90.025
N.Empty.Lc/BV (N/mm2)13.6 ± 9.639.9 ± 16.1<.001
Tt.Lc.V/BV (%)1.616 ± 0.3891.429 ± 0.3270.019
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Figure 1. Increased osteocyte death after PTX. Bone histology of a representative patient with secondary hyperparathyroidism before and after PTX is shown. The two regions indicated by the blue squares are highlighted in the lower panels (magnification ×400). Note that live osteocytes reside in the lacunae (red arrows) before PTX, whereas many lacunae are empty and devoid of osteocytes (yellow arrows) at 3 weeks after PTX.

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Figure 2. Reduction in osteocyte lacunar volume after PTX. Bone histology of a patient with secondary hyperparathyroidism before and at 4 weeks after PTX (upper panels) along with their schematic illustrations (lower panels). Note the reduced volume of the osteocyte lacunae as well as the many empty lacunae following PTX. Some osteocytes died (red arrowhead) in response to a rapid reduction in PTH after PTX, whereas others remained alive or recovered (yellow arrowhead) and possibly were involved in the mineralization that took place around them (4 weeks after PTX).

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Mineralization around osteocyte lacunar walls and canaliculi

We found that tetracycline labeling was observed not only at the mineralization front on the bone surface but also around the osteocyte lacunar walls and canaliculi (Fig. 3) within both the BMU and BSU after PTX (Fig. 4), prompting us to hypothesize that mineralization was taking place along the lacunocanalicular system after surgery. We calculated and evaluated tetracycline-labeled areas separately at the mineralization front (MF-TC.V/BV/day) and around the osteocyte cell bodies and canaliculi in the BMU (Ot-TC.V in BMU/BV/day) and the BSU (Ot-TC.V in BSU/BV/day).

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Figure 3. Mineralization around osteocytes and along osteocyte canaliculi after PTX. Bone histology of a patient at 4 weeks after PTX (left) with a schematic illustration (right). Note the tetracycline labeling around the osteocytes and along the osteocyte canaliculi. Magnification ×400.

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Figure 4. Diffuse mineralization inside bone after PTX in patients with secondary hyperparathyroidism. Bone histology of two representative patients at 4 weeks after PTX (middle and right panels) and a hemodialysis patient with low PTH exhibiting adynamic bone disease (left, upper panel) along with their schematic illustrations (lower panels). Note that tetracycline labeling was observed diffusely in both the BMU and the BSU after PTX in patients with secondary hyperparathyroidism (middle and right panels), whereas very little labeling was exhibited in the BSU of a patient with adynamic bone disease (left panels). Magnification ×200.

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As shown in Table 4, the percentages of tetracycline-labeled areas were 0.135 ± 0.056%/day at the mineralization front, 0.039 ± 0.023%/day around the osteocytes in the BMU, and 0.282 ± 0.217%/day around the osteocytes in the BSU after PTX, indicating that osteocyte-based tetracycline labeling in the BSU was much greater than that in the BMU (p < .001) and at the mineralization front (p = .020).

Table 4. Increased Tetracycline Labeling Around Osteocytes After PTX
VariablesPTX group (n = 16)Low-PTH control group (n = 7)pHigh PTH control group (n = 7)p
  1. Note: In iliac bone biopsy specimens obtained at 2 to 4 weeks after PTX, tetracycline labeling was assessed at three distinct locations: mineralization front (MF) and around osteocytes and canaliculi (Ot-TC) within the BMU and the BSU, as described under “Materials and Methods.” Hemodialysis patients with low PTH and secondaty hyperparathyroid patients with high PTH without PTX served as control groups. All values are expressed as means ± SD.

MF-TC.V/BV/day (%/day)0.135 ± 0.0560.017 ± 0.032<.0010.220 ± 0.0740.006
Ot-TC.V in BMU/BV/day (%/day)0.039 ± 0.0230.003 ± 0.003<.0010.021 ± 0.0040.051
Ot-TC.V in BSU/BV/day (%/day)0.282 ± 0.2170.005 ± 0.0060.0030.017 ± 0.0110.004

In the low-PTH control group, which included 7 patients diagnosed with ABD, tetracycline labeling was markedly decreased at all three locations compared with the study group after PTX (Fig. 4, Table 4). In the high-PTH control group, which included 7 patients with high PTH but no PTX, osteocyte-based tetracycline labeling in the BSU was markedly decreased, whereas osteoblast-mediated mineralization on the bone surface was significantly increased compared with the study group after PTX (Table 4).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

It is demonstrated in this study that along with a marked reduction in circulating PTH levels following PTX, osteocyte number and lacunar volume decreased, and empty lacunae increased significantly compared with pre-PTX levels, which together suggest that with the functional importance of the PTH receptor abundant in osteocytes,16, 17 osteocyte death took place after PTX, presumably owing to decreased PTH signaling in osteocytes.

In parallel, we have made intriguing observations that at 2 to 4 weeks following PTX, tetracycline labeling around osteocytic lacunae and along the canaliculi increased markedly, especially in the BSU (rather than at the mineralization front and within the BMU) compared with the low-PTH and high-PTH control groups without PTX. Since direct comparison of labeling between pre- and post-PTX in the same patients was not possible, we recruited the high-PTH control group without PTX. A limitation of this study is that the high-PTH control group had less severe hyperparathyroidism than the PTX group on the basis of PTH levels. Thus our results are consistent with, but do not prove, the concept that the decline in PTH levels following PTX is related to the increased mineralization. Also, since tetracycline labeling was not increased in the low-PTH control group, where the PTH levels were maintained at a chronically low level, we believe that the abrupt decrease in PTH levels following the surgery is responsible for the increased mineralization as well as osteocyte death.

The relationship between the increased osteocyte death and the increased mineralization around the osteocyte-canalicular system, and whether there exists a cause-and-effect relation between the two events, is not clear at present. Osteocytes are believed to differentiate from osteoblasts,18 and whether osteocytes are actively involved in mineralization is a subject of debate.19 During the terminal differentiation process of osteocytes, matrix-producing osteoblasts are buried in the unmineralized matrix as osteoid osteocytes, which then become mature osteocytes as the surrounding matrix becomes mineralized.9, 20 It has been reported that newly formed woven bone contains four to eight times more osteocytes than older lamellar bone in osteoporotic patients,21 and we observed (as shown in Fig. 5) that before PTX for secondary hyperparathyroidism, both the BMU and the BSU contained abundant woven bone where osteocytes were enriched,11, 22 which is presumably ascribed to the sustained high level of PTH. Following PTX, in contrast, mineralization increased in the BMU and more so in the BSU that contained fewer osoteocytes, which may be accounted for by the sudden drop in PTH levels. The diffuse pattern of mineralization in the BSU observed after PTX (Fig. 4) may be explained by the criss-cross texture of woven bone characteristically observed in renal hyperparathyroidism before PTX.22

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Figure 5. Abundant osteocytes in woven bone in secondary hyperparathyroidism before PTX. Bone histology of a patient with secondary hyperparathyroidism before PTX. The region indicated by the yellow square is highlighted in the lower panels (magnification ×100). Note the enrichment of osteocytes in the woven bone area (blue arrow) compared with those in the lamellar bone area (yellow arrow). The lamellar and woven nature of bone is shown under polarized light (lower right panel).

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The loss of osteocytes has been associated with an accumulation of microdamage,8, 14 and accordingly, osteocyte lacunar density has been reported to be lower in subjects with fracture than in those without fracture and to correlate inversely with crack density.14, 23 While it would follow that the reduced osteocyte number at 2 to 4 weeks after PTX predisposes to increased bone fragility, the longer-term consequences of PTX on skeletal health are not known, and the increased mineralization over a wide area, especially in the BSU, could have a protective role against fracture after PTX.

In agreement with our previous reports,10–12 the bone surface covered with osteoclasts almost disappeared at 2 to 4 weeks following PTX, with marked decreases in the biochemical markers of bone resorption (Tables 1 and 2). It is tempting to speculate that the increased deposition of calcium along the osteocyte-canalicular system, together with the markedly decreased activity of osteoclastic bone resorption and delayed inhibition of mineralization on the bone surface, may contribute to hypocalcemia that is a frequent complication after PTX.

In conclusion, the osteocyte number and function in chronic kidney disease, especially in the high-PTH milieu before PTX and following the abrupt decrease that occurs after PTX, may have substantial impact on bone metabolism and quality. Further investigation is warranted to better understand the mechanism of increased bone fragility in patients with chronic renal failure.

Disclosures

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

All the authors state that they have no conflicts of interest.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

We thank the staff of the Ito Bone Histomorphometry Institute (Niigata, Japan) for excellent technical assistance. This study was supported in part by a grant-in-aid for longevity science from the Ministry of Health, Labor and Welfare of Japan (to KI). Part of this work was presented at the Scientific Exhibition of the American Society of Nephrology in Philadelphia, PA, USA, in 2008. Pacific Edit reviewed the manuscript prior to submission.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References