Osamu Otsubo

Changes of bone remodeling immediately after parathyroidectomy for secondary hyperparathyroidism

BACKGROUND Successful parathyroidectomy for secondary hyperparathyroidism alleviates bone pain and is followed by the development of hypophosphatemia and hypocalcemia, as well as an increase in bone mineral density. An increase in osteoblast surface (Ob.S/BS) is not observed several months after surgery. In this study, we investigated early bone changes at 1 week after parathyroidectomy and the mechanism underlying an increase in bone mineral density. METHODS Fourteen patients with severe secondary hyperparathyroidism underwent iliac bone biopsy before and 1 week after parathyroidectomy. Changes in histomorphometric parameters, including osteoclast surface (Oc.S/BS), eroded surface (ES/BS), erosion depth (E.De), fibrosis volume (Fb.V/TV), Ob.S/BS, osteoid volume (OV/BV), osteoid surface (OS/BS), and osteoid thickness (O.Th), were investigated. Changes in texture of mineralized bone and osteoid seams were also investigated. RESULTS Oc.S/BS (P < 0.001), ES/BS (P < 0.01), and E.De (P < 0.001) decreased, but Fb.V/TV did not change at 1 week postoperatively. In particular, osteoclasts disappeared in almost all patients. Ob.S/BS (P < 0.001) increased, and cuboidal osteoblasts were proliferating on the trabecular surface where osteoclasts had existed before parathyroidectomy. As a result, newly developed osteoblasts coexisted with fibrous tissue after surgery. OV/BV (P < 0.005), OS/BS (P < 0.005), and O.Th (P < 0.005) increased, with lamellar osteoid volume showing a particular increase. Bone mineralization continued despite the low postoperative serum parathyroid hormone level. CONCLUSION A rapid decrease in serum parathyroid hormone level after parathyroidectomy appears to suppress bone resorption, as well as cause a transient marked increase in bone formation and an increase in normal lamellar osteoid seams.

Development of low-turnover bone diseases after parathyroidectomy and autotransplantation

Abstract Parathyroidectomy and immediate autotransplantation (PTX‐AT) has been shown to decrease bone pain and increase bone mineral density. However, adynamic bone disease (ABD) has been predicted to develop if the serum intact parathyroid hormone (i‐PTH) level remains lower than normal for a long period of time. Therefore, we investigated the bone histology of patients whose serum i‐PTH levels did not increase over 70 pg/mL for 1 year after PTX‐AT. Four chronic hemodialysis patients were investigated. The serum intact osteocalcin (i‐OC) level was measured and histomorphometry for cancellous bone was performed 1 year after the operation. Tetracycline hydrochloride was administered in the 12 weeks after PTX‐AT. The serum i‐PTH levels were 20.5 ± 15.0 pg/mL and i‐OC levels were 19.5 ± 0.9 ng/mL. Histomorphometric analyses showed the osteoclast surface to be 0.1% in two cases and 0% in the other two cases, the eroded surface was 7.7 ± 6.1%, and the fibrosis volume and osteoblast surface were 0% in all four cases. Osteoid volume, osteoid surface and osteoid thickness were lower in cases 1–3, but higher in case 4. All tetracycline labelings were in contact with the mineralization front in cases 1 and 3, but some were not in cases 2 and 4. Serum i‐PTH and i‐OC levels indicated that ABD developed in these four cases. Histomorphometric analyses revealed that ABD developed in case 1, while either ABD or low‐turnover osteomalacia developed in cases 2 and 4, and low‐turnover osteomalacia was observed in case 3 after PTX‐AT. In conclusion, i‐PTH should not be maintained at lower levels to avoid low‐turnover bone diseases.

Characteristics of Patients on Hemodialysis Therapy for More Than 30 Years

Abstract:  Since its experimental introduction in 1960, hemodialysis has become a widely performed and relatively safe procedure. Therapeutic strategies have been developed, and the numbers of long‐term survivors of hemodialysis therapy have been increasing. Hemodialysis therapy was introduced at Sangenjaya Hospital in October 1970, and the 16 patients who have survived for more than 30 years on hemodialysis therapy since its introduction at the hospital were enrolled in this study to investigate the characteristics of long‐term hemodialysis patients. For comparison, 50 patients on hemodialysis for less than 30 years were also studied (21 patients with <10 years hemodialysis, 13 with 10–20 years hemodialysis and 16 with 20–30 years hemodialysis). Background information (age, gender, and cause of renal disease), dialysis dose (single pool [sp.] Kt/V), mineral metabolism (serum phosphate), anemia management (serum hemoglobin), and nutrition (serum albumin and reduced interdialytic weight gain) were assessed. Hemodialysis was instituted at 28.7 ± 6.4 years of age. The primary cause of end‐stage renal disease was chronic glomerulonephritis in all of the patients except one, and in that patient it was polycystic kidney disease. As an index of the dialysis dose, sp. Kt/V was 1.2 ± 0.11. As an index of mineral metabolism, serum phosphate was 5.4 ± 0.9 mg/dL. As an index of anemia management, serum hemoglobin was 10.2 ± 1.2 g/dL. As indexes of nutrition, serum albumin was 4.0 ± 0.2 g/dL and interdialytic weight gain was 4.43 ± 1.36%. The sp. Kt/V‐value, serum phosphate, serum hemoglobin and interdialytic weight gain did not differ between the four different hemodialysis duration groups. Serum albumin was lower in the >30 group (4.0 ± 0.2 g/dL) than in the <10 group (4.2 ± 0.3 g/dL) (P = 0.046). As the duration of hemodialysis has increased, the age at hemodialysis induction has become younger. The cause of the renal failure was chronic glomerulonephritis in most of the cases. None had diabetic nephropathy. Improvement of the prognosis of patients with diabetic nephropathy is required. Most of the indexes of these patients nearly satisfied the recommended values.

Mult-component analysis of urine of dogs with liver diseases by high-performance liquid chromatography

Components of the urine of normal dogs and dogs with liver diseases were analysed by high-performance liquid chromatography (HPLC) using a macroreticular anion-exchange resin with UV detection. The dogs with liver diseases were experimentally prepared by either Eck fistula by portal-caval anastomosis, dimethylnitrosamine-induced liver failure or total hepatectomy by operation. Eighteen chromatographic peaks were numbered and the cross-correlation coefficient of the intensities of every pair of peaks was computed. There were high correlations between several pairs of peaks according to the types and degrees of the hepatic failures, whereas no significant correlation was observed for the peak pairs of normal urine samples. The results showed that HPLC analysis of urine is useful in the diagnosis of the physiological state in liver dysfunction.

A New Method for Early Detection of Renal Allograft Rejection

We developed a new device utilizing high-performance chromatography to measure urinary IgM protein in renal transplant recipients. With this device we were able to obtain a reliable result in less than 2 h, requiring much less time than using the conventional method. Urinary IgM was found in 22 of 23 posttransplantation patients (96%) during acute rejection. An increase in urinary IgM excretion was noted 2-3 days before the appearance of clinical signs of acute rejection.