Early Skeletal Effect of Alkali Therapy upon the Osteomalacia of Renal Tubular Acidosis

Abstract

The administration of alkaline agents to a 16-year-old girl with severe renal tubular acidosis and osteomalacia caused an almost immediate rise of the urinary excretion of total hydroxyproline. The increment of the dyalizable fraction predominated over the nondyalizable component. Gradually serum phosphate and serum alkaline phosphatase increased whereas urinary calcium and magnesium and phosphate clearance declined. Serum PTH remained elevated throughout. We suggest that the correction of the metabolic acidosis might increase the transport of phosphate and calcium across the functional bone membrane leading to a rapid deposition of lime salts in the uncalcified matrix with a concomitant increase in bone collagen turnover.

Chronic metabolic acidosis increases the serum concentration of 1,25-dihydroxyvitamin D in humans by stimulating its production rate. Critical role of acidosis-induced renal hypophosphatemia.

“…Third, rats with chronic mineral acidosis and associated hypophosphatemia exhibit increased bone resorption as well as decreased bone formation (59,60). Fourth, hypophosphatemia is often present during chronic acidosis of either renal tubular or extrarenal etiology (59,60) and the reversal of skeletal lesions by alkali treatment alone is associated with a markedly positive phosphate balance (3,5 …”

“…Metabolic acidosis profoundly affects calcium and phosphate metabolism resulting in calcium losses from bone ( 1 ) in association with hypercalciuria. Important clinical sequelae are a metabolic bone disease resembling osteomalacia (2)(3)(4)(5)(6)(7)(8) and calcium nephrolithiasis (9).…”

Attainment and Maintenance of Normal Stature with Alkali Therapy in Infants and Children with Classic Renal Tubular Acidosis

“…In children with classic RTA, impaired growth is frequently associated with frank rickets or osteopenia (1, 21, 23-25, 27, 70). The bone disease of both children and adult patients with untreated classic RTA is predictably healed with alkali therapy alone (7,23,27), and it would appear that the healing process can begin almost immediately after alkali therapy is initiated (70 Table I. …”

Acquired alterations in vitamin D metabolism in the acidotic state

“…The observation that alkali therapy alone normalizes the growth rate [3] and heals the rickets [4][5][6] in patients with type I RTA suggests a possible causal relationship between acidosis and the growth, modeling, and remodeling of bone [3,[7][8][9][10]. It has been proposed that the pathogenesis of growth failure in infants and children with untreated type I RTA includes an acidosis-dependent impairment in the renal conversion of 25-hydroxycholecalciferol (25OHD3) to 1,2.,-dlhydr,,xy ..... e,,dc.fero, t.,~-5~OH~zDzJ, and perhaps to other biologically active metabolites of 25OHDz as well [3].…”