Conservative management of metabolic derangements in osseous tissue among patients with vitamin d-dependent rickets type 2

Stepan Martsyniak; Tamara Kincha-Polishchuk

doi:10.1530/boneabs.6.P056

Objectives: To determine the influence of conservative management upon genetically-determined metabolic derangements in osseous tissue among patients with vitamin D-dependent rickets type 2.

Methods: The conservative management of the 39 patients with rickets-like diseases involved 4 stages (tab1). 1st stage included complete examination of the patient referring determination of the calcium and phosphorus in blood and urine, calcidiol and calcitriol in blood, parameters of parathyroid hormone and osteocalcin as well as marker of bone formation P1NP and that of bone resorption B-CTx. At the first stage, it was obligatory for all children to go through genetical testing. The goal of the study was detection of alterations (polymorphism) in the alleles of receptors to vitamin D (VDR) and to collagen type 1 (COL1). Examinations and correlations (tab. 2,3) at the next stages were conducted completely except genetical studies.

Results: Comprehensive study of vitamin D metabolism and biochemical parameters of osseous tissue’s vital activity among patients with VDDR type 2 allowed us to have fundamentally studied some points in the pathogenesis and nature of osteomalatic and subsequently osteoporotic alterations at the deferent extent.

Summary & Conclusion: On the ground of biochemical parameters’ study among the patients with vitamin D-dependent rickets type 2 we developed pathogenetically-substantiated effective pharmacological therapy of orthopedic manifestations. The therapy is based upon administration of higher doses of vitamin D (up to 70000 U/month at the first stage, then down to 45000 U/month) and alfacalcidol (up to 1 μg/month at the onset of treatment) for activation of receptors to vitamin D (VDR). Subsequently, the management does not require high doses of vitamin D. For the achievement of therapeutic effect in treatment of orthopedic manifestations in rickety process level of the hormonal form of vitamin D (calcitriol) should be limited within range 250–350 ng/ml (P < 0.05). There is no reason to use alfacalcidol for pharmacological treatment of VDDR type 2.

Table 1 Average measures of osseous metabolism among examined patients with VDDR type 2.
	Stage of treatment
	Stage 1	Stage 2	Stage 3	Stage 4
Indices of bone metabolism	M±m	M±m	M±m	M±m
Ca+	1.24±0.0097	1.28*±0.0104	1.28*±0.0154	1.32*±0.0087
P	1.71±0.0309	1.637368±0.0583	1.724±0.0336	1.79±0.1579
Ca	2.51±0.0158	2.57**±0.0257	2.58**±0.0250	2.60**±0.0452
25(OH)D	34.51±3.3952	68.05*±4.9992	77.60*±8.3518	73.18*±20.2909
1,25(OH)₂D	149.92±8.8943	276.79*±22.6938	296.60*±24.7957	306.50*±35.7736
PTH	32.87±2.6910	25.20**±3.2285	23.45**±2.9311	24.125±4.0828
Osteocalcin	33.90±4.9894	16.19*±2.0041	15.65**±2.0247	19.45±4.1949
Urine calcium (daily)	1.74±0.1288	2.047895±0.3555	1.4±0.2658	1.4225±0.4731
Urine phosphorus (daily)	17.16±1.6125	14.72105±1.5853	11.55±0.8034	9.05**±0.9350
P1NP	895.82±41.2641	662.95*±46.7270	567.6*±35.3347	583.25*±31.7579
B-CTx	1.51±0.0685	1.14*±0.0910	1.01*±0.1072	1.10*±0.1871
* - significant difference of the parameter comparing to the 1^st stage of treatment (P < 0.05)** - trend close to significant difference of the parameter comparing to the 1^st stage of treatment (0.1 > P > 0.05).

Table 2 Correlation between blood and urine parameters among the patients with VDDR type 2 (before the treatment).

Table 3 Correlation between blood and urine parameters among the patients with VDDR type 2 (after the 1st therapeutic stage).

Disclosure: The authors declared no competing interests.

Bone Abstracts

P056