Bone disease post txp

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Hortense Ferguson
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2 Bone disease post txp Disturbances in bone metabolism are common complications that affect patients after successful renal transplantation Post-transplantation bone disease is distinctly different from common forms of osteoporosis. Three major components contribute to bone metabolic disturbances in patients after renal transplantation: pre-existing renal osteodystrophy at time of renal transplantation effects and consequences of transplantation-specific therapies on bone the effects of reduced renal function after renal transplantation.

3 Renal osteodystrophy Is classified into four major groups: high turnover bone disease adynamic or low turnover bone disease mixed renal osteodystrophy osteomalacia

4 Cortical vs cancellous bone Two critical functions of the bone: Mechanical strength and mineral metabolic activity Mechanical function of the bone is served mainly by cortical bone, disurbance in cortical bone function causes fractures. Metabolic function of the bone is served mainly by cancellous bone, disturbance in cancellous bone function results in inability to maintain mineral homeostasis. Loss of cortical bone occurs mainly in patients with high turnover bone disease loss of cancellous bone is often seen in patients with low bone turnover.

5 Type Histopathologic features Biochemical abnormalities Hyperactive (high turnover) bone disease Adynamic (low turnover) bone disease Mixed renal osteodystrophy Osteomalacia in bone turnover irreg shaped trabecules num of bone cells with irregular arrangement and shape bone volume and mineralization in bone formation. presence of few osteoid and few osteoblasts. Osteoclast number may be low, normal, or high Defective mineralization +/- bone formation and PTH activity in bone. num of heterogeneous remodeling sites Num of osteoclast. Bone volume is variable and depends on a dominant pathogenic cause accumulation of unmineralized matrix in which a in mineralization precedes or is more pronounced than the inhibition of collagen PTH alkphos varying levels of calcium and phos 1,25(OH)2D level to normal PTH alkphos varying levels of phos. calcium tends to be high varying 1,25(OH)2D level PTH Alkphos varying levels of calcium and phos levels varying 1,25(OH)D level Varying levels of PTH, alkphos, calcium and phos.; usually 1,25(OH)2D and 25(OH)D levels Clinical consequences Bone pain risk of fracture; graft loss risk? risk of vascular calcification mortality risk? vascular calcifications?; risk of fracturle? Bone pain risk of fracture?; mortality and graft loss risk? risk of fracture? risk of osteoporosis; bone pain and discomfort

6 Bone disease Low tunover bone disease: No osteoid, arrow showing one osteoclast Low tunover osteomalacia: High osteoid volume, no osteoclast or osteoblast

7 Prospective study following 20 patients who received LDKT for 18 months post transplant. Pts treated with azathioprine, CSA and low dose prednisone Determined BMD of second, third and fourth lumbar vertebrae and shaft of radius Iliace bone biopsy at the time of transplant and 6 months after.

10 Biopsy findings Prospective study 57 posttransplant patients underwent biopsy on average at 5.6 yrs post kidney transplant Before biopsy they underwent double tetracycline labeling Bone biopsy taken from ant iliac crest

13 glucocorticoids Canalis E et al. Ann N Y Acad Sci 2002; 966:73 81.

15 Glucocorticoids effect on osteoblasts Prospective study 20 patients Iliac bone biopsy and double tetracycline staining performed before and after transplant Rojas E et al. Kidney Int 2003; 63:

16 Rojas E et al. Kidney Int 2003; 63:

17 Rojas E et al. Kidney Int 2003; 63:

18 Rojas E et al. Kidney Int 2003; 63:

19 Rojas E et al. Kidney Int 2003; 63:

20 Calcineurin inhibitors Prospective, included 86 transplant patients 65 on tacrolimus-based immunosuppression and 21 on cyclosporinebased immunosuppression BMD measurements in lumbar spine (L2 L4) and femoral neck in the first month after transplantation (baseline) and yearly thereafter up to the fourth year. Marcen R et al. Transplantation 2006; 81:

21 Lumbar spine BMD Femoral neck BMD Marcen R et al. Transplantation 2006; 81:

22 Calcineurin inhibitors Twelve 8-week-old male Sprague- Dawley rats rats were randomly divided into two groups and were intraperitoneally injected with either FK506, at a dose of 1mg/kg per day (FK506-treated group; n 7) or physiological saline (control group; n 5) for the duration of the 5-week experiment. Kirino, S. et al. J. Bone Miner. Metab. 22, (2004).

23 Kirino, S. et al. J. Bone Miner. Metab. 22, (2004).

24 Risk of fracture Retrospective study 1572 kidney transplants done at a single center between February l963 and May /-5.4 years of follow-up. O'Shaughnessy, E. A. et al. Transplantation 74, (2002).

25 O'Shaughnessy, E. A. et al. Transplantation 74, (2002).

26 O'Shaughnessy, E. A. et al. Transplantation 74, (2002).

27 O'Shaughnessy, E. A. et al. Transplantation 74, (2002).

28 Thank You

BULLETIN. Slovak Republic Ministry of Health

BULLETIN. Slovak Republic Ministry of Health BULLETIN Slovak Republic Ministry of Health Part 51-53 November 13, 2009 No. 57 CONTENTS: 52. Slovak Republic Ministry of Health Guidelines for the Diagnosis of Glucocorticoidinduced Osteoporosis 52. Slovak