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mineral bone disorder in CKD:

mineral bone disorder in CKD Dr Mohammed Abdelsattar

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Enhanced PTH synthesis/secretion occurs in response to hypocalcemia , hyperphosphatemia , and/or a decrease in serum 1,25-dihydroxyvitamin

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concentrations of PO 4 and Ca 2+ are maintained through interaction between PTH, 1,25(OH) 2 D ( calcitriol ), fi broblast growth factor-23

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high serum levels of calcium or calcitriol or FGF-23 suppress PTH synthesis Secretion extracellular concentration of ionized calcium is the most important determinant of the minute-to-minute secretion of PTH

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Calcitonin is therefore the physiological antagonist of PTH . The two hormones act in concert to maintain normal concentration of calcium ion in the extracellular flui d

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recommend monitoring serum levels of calcium, phosphorus, PTH, and alkaline phosphatase activity beginning in CKD stage 3 (1C) In children we suggest such monitoring beginning in CKD stage 2 (2D)

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mathematical construct of the calciumphosphorus product ( CaP ) is of limited use in clinical practice, as it is largely driven by serum phosphorus and generally does not provide any additional information beyond that which is provided by individual measures


FGF23 FGF23 is a bone-derived hormone that regulates systemic phosphate, vitamin D metabolism FGF23 inhibits renal tubular reabsorption of phosphate reduces circulating 1, 25(OH) vit D Elevated FGF23 levels are responsible for hereditary and acquired hypophosphatemic rickets disorders FGF23 has been proposed to be the initial adaptive response leading to reductions in 1,25(OH)D and secondary hyperparathyroidism in CKD

High-turnover Bone Disease:

High-turnover Bone Disease   overactivity of the parathyroid gland   include retention of phosphates, hypocalcemia , decrease in 1,25 dihydroxyvitamin D level, skeletal resistance FGF23 may indirectly promote hyperparathyroidism as it further inhibits production of 1,25-dihydroxyvitamin D

ABD is characterized by :

ABD is characterized by low-bone turnover without osteoid accumulation with a thin osteoid seam .

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Both the rate of collagen synthesis by osteoblasts and the subsequent mineralization of bone collagen are subnormal. The latter distinguishes ABD from the second low-turnover form, i.e. osteomalacia , where a mineralization defect exceeds the defects in bone formation, resulting in a relative osteoid excess

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minimal or no peritrabecular fibrosis or marrow Fibrosis in contrast to osteitis fibrosa Patients with reduced bone turnover exhibited a higher systemic calcium exposure increase risk of soft tissue and vascular calcifi cation .

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Bone alkaline phosphatase is probably the single most useful biochemical parameter for the assessment of bone formation. Elevated levels of bone alkaline phosphatase exclude an adynamic renal bone disease elevations of BAP along with may be seen in cases of severe osteomalacia

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Although low turnover disease is common in the absence of aluminum, it was initially described as a result of aluminum toxicity Aluminum bone disease is diagnosed by special staining, which demonstrates the presence of aluminum deposits

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 The histologic pattern of ABD is generally associated to low levels of PTH However, PTH serum levels in CKD are generally higher than normal even when associated to ABD.

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 ABD is frequently characterized by skeletal resistance to bone-anabolic PTH actions presumably via a down-regulation of the PTH/ PTHrp receptor on osteoblasts


Osteomalacia Osteomalacia is characterized by an excess of unmineralized osteoid , manifested as Wide osteoid seams and a markedly decreased mineralization rate

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absence of cell activity and the absence of endosteal fibrosis there is normal or decreased osteoid volume and decreased mineralization aluminum disease is associated with osteomalacia And cause osteomalacia like picture

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Aluminum intoxication prevent deposition of Ca At mineralization sites So may increase in blood cause suppression of parathyroid hormone

Difference Between Osteoporosis and Osteomalacia :

Difference Between Osteoporosis and Osteomalacia Osteoporosis :Bone mass reduced , mineralisation normal Osteomalacia :Bone mass variable , Mineralisation decreases   Age at onset  Osteoporosis elderly and postmenopausal   Osteomalacia Any age  

TTT of high turnover dse:

TTT of high turnover dse phosphorus control vitamin D treatment Calcimimmetics parathyroidectomy

Dietary restriction:

Dietary restriction Dietary phosphorus restriction must be prescribed at all stages of renal failure in adults It may be achieved by decreasing protein intake and avoiding foods rich in phosphorus

Phosphate binders:

Phosphate binders Taken with meals to bind phosphate in the gut T ypes Aluminium hydroxide Calcium-containing phosphate binders Non-calcium non- aluminium -containing binders

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Aluminium hydroxide is the most effective binder but potential aluminium toxicity (skeletal and neurological) restricts its use <4 weeks

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Calcium-containing phosphate binders bind PO 4 , but correct Ca 2+ suppress PTH contributors to vascular calcification Non-calcium-based binders are preferred in patients with severe vascular or soft tissue calcifications

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Non-calcium, non- aluminium -containing binders e.g. sevelamer hydrochloride ( Renagel R ) or carbonate ( Renvela R ) and lanthanum carbonate ( Fosrenol R ) more expensive than calcium or aluminium based binders. Equally as effective as CCPBs Sevelamer lowers LDL cholesterol and may provide additional CV risk reduction

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Magnesium-calcium combination binders e.g. calcium acetate magnesium carbonate Osvaren

Adequate dialysis:

Adequate dialysis Poor PO 4 control may be an indication for more frequent dialysis. Daily dialysis regimens can control PO 4 , with no binder requirement

vitamin D treatment:

vitamin D treatment Once PO 4 controlled, add alfacalcidol or calcitriol , titrating the dose to achieve a locally agreed target PTH Using the 1 A - hydroxylated analogues calcitriol or alfacalcidol 1 A - calcidol Newer vitamin D analogues e.g. paricalcitol or doxercalciferol Start with a low dose 0.25 micrograms/day alfacalcidol PO


calcimimetics control of extracellular Ca 2+ concentration and regulation of steady state PTH secretion Small molecules that bind to the parathyroid CaR and mimic the effect of i extracellular Ca 2 reductions in PO 4 a NICE guideline in the UK effectively restricts their use to refractory i PTH where parathyroidectomy is contraindicated

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M impra-sensipar 30mg od , increased incrementally 60mg, 90mg,120mg, 180mg), as necessary, to maintain target PTH after starting treatment and after any dose change. Hypocalcaemia may require dose reduction. Ca 2+ usually checked monthly for fi rst 6 months and PTH 2 – 3-monthly


parathyroidectomy bone biopsy should be considered prior to proceeding with parathyroidectomy Tertiary or autonomous hyperparathyroidism Manifests clinically as i ncrease PTH (usually >500pg/ mL ), with persistent increase in Ca 2+ If calcium is low or normal, i ncrease PTH indicates SHPT , and further medical treatment is necessary.

Management of the patient with ABD :

Management of the patient with ABD Adynamic bone disease in stage 5 CKD (determined by bone biopsy or iPTH concentrations < 100 pg/ml should be treated by allowing plasma iPTH concentrations to increase in order to increase bone turnover This can be accomplished by decreasing dosages of calcium-based phosphorus binders and vitamin D or eliminating such therapy

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two principles first to reduce calcium and vitamin D load second, to restore PTH activity

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  lowering dialysate calcium concentration improves ABD Reducing the dialysate calcium concentration from 1.75 or 1.5 mmol /L to 1.25 mmol /L reduced serum ionized calcium, diminished episodes of iPTH hypercalacemia and increased Avoidance of vitamin D over-treatment The administration of active vitamin D compounds reduces bone turnover in CKD patients

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Teriparatide as a bone-stimulating agent confirmed ABD patients with fracturing osteoporosis daily subcutaneous application of PTH(1–34), teriparatide , is a powerful anti-osteoporotic treatment. In theory, teriparatide offers the chance to restore bone metabolism in patients with ABD

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aluminum disease is associated with osteomalacia . Serum PTH is, in general, normal or low , and hypercalcemia is common. Looser zones or pseudofractures are radiologic characteristics

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Aluminium removal in cases of significant exposure Desfroxamine mobilizes aluminium from bone and decreases the proportion of protein-bound aluminium in plasma, thereby facilitating removal by dialysis

Hungry bone syndrome:

H ungry bone syndrome In patients with hyperparathyroidism and severe bone disease who undergo successful parathyroidectomy hypocalcaemia may be severe and parenteral calcium infusion with later supplementation with oral calcium and vitamin D .


calcification Aside from the negative skeletal effects of secondary HPT, soft tissue calcification can occur in other body tissues, including the skin and subcutaneous tissue, cornea and conjunctiva, muscle, lung, GIT, CVS. Calcification of cardiac tissue can affect the myocardium, the conduction system, and valves, and thus may cause adverse cardiovascular events


sources Oxford in nephrology and htn Nephrology secrets Harrison internal medicine http://ckj.oxfordjournals.org KDIGO guidelines

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