Vol 21, No 2 (2018)

Original study
Antiresorptive activity of denosumab in the treatment of osteoporosis in patients with rheumatoid arthritis
Banshchikova N.Y., Letyagina Y.A., Omelchenko V.O., Korolev M.A.

Background: fracture risks assessment and determination of bone mineral density are modern methods, generally accepted and widely used. However, they have limitations and disadvantages for the dynamic evaluation of bone remodeling processes in RA-patients with low BMD. The investigation of bone resorption markers is an important issue.

Aims: to compare the antiresorptive activity of denosumab and alendronic acid in patients with rheumatoid arthritis and osteoporosis using β-CTX and osteocalcin (OC).

Materials and methods: forty-two patients were included in the study (16 patients were treated with denosumab, 13 patients – with alendronic acid, 13 patients - control group without any osteoporosis treatment). The quantitative determination of β-CTX and OC as well as dual-energy X-ray absorptionometry (DXA) were carried out for all patients at the first visit with consecutive investigation of bone resorption markers 3 months after. The predictive capacity was determined using the ratio of observed fractures/expected fractures by FRAX.

Results: The level of β-CTX 16% (median 861.6 pg/ml vs. 724.6 pg/ml, p = 0.049) and OC 39% (median 13.9 ng/ml vs 8.5 ng/ml, p = 0.047) decreased significantly in 3 month in RA patients treated with denosumab. The decrease of β-CTX (median 858.9 pg/ml vs. 821.8 pg/ml) and OC (median 14.8 ng/ml vs. 13.9 ng/ml) was observed in the group of patients treated with alendronic acid, but not reached statistical significance.

Conclusions: denosumab had showed better antiresorptive activity compared with bisphosphonates, which was registered 3 month after the start of the treatment.

Osteoporosis and Bone Diseases. 2018;21(2):4-11
The effectiveness of nutritional vitamin D supplementation and selective vitamin D receptor agonists treatment on secondary hyperparathyroidism in chronic kidney diseases patients
Egshatyan L.V., Mokrisheva N.G.

Background: secondary hyperparathyroidism (SHPT) is an early complication of chronic kidney disease (CKD). Maintaining the level of 25(OH)D and parathyroid hormone concentrations in the target range reduce its associated complications (fractures and cardiovascular calcification).

Aims: to examine the effectiveness of vitamin D supplementation and selective vitamin D receptor agonists treatment on SHPT in CKD.

Material and methods: prospective observational study to evaluate the efficacy and safety of vitamin D therapy SHPT in 54 in patients with CKD. The first phase (24 weeks) – treatment of suboptimal 25-hydroxycalciferol (25(OH)D) levels. The second (16 weeks) – treatment colecalciferol-resistant SHPT by combination of cholecalciferol with paricalcitol. Blood samples were taken to assess parathyroid hormone (PTH), 25(OH)D, creatinine, calcium, phosphorus levels and calcium excretion.

Results: After 8 weeks of cholecalciferol treatment all patients achieved 25(OH)D levels above 20 ng/ml, however 78% of patients still had SHPT. After 16 weeks, the decrease of PTH was achieved in all patients, but significantly only in patients with CKD 2 (19.2%, p< 0.01) and 3 (31%, p <0.05), compared with CKD 4 (17%, p >0.05). After 24 weeks of therapy, PTH normalized in all patients with CKD 2, in 15 (79%) with CKD 3 and in 9 (50%) patients with CKD 4. Cholecalciferol treatment resulted in a substantial increase in 25(OH)D levels with minimal or no impact on calcium, phosphorus levels and kidney function.

After 24 weeks we initiated combination therapy (cholecalciferol and paricalcitol) for patients with colecalciferol-resistant SHPT (n=13). PTH levels decreased from 149.1±13.4 to 118.2±14.1 pg/ml at 8 weeks, and to 93.1±9.7 pg/ml (p <0.05) at 16 weeks of treatment. No significant differences in serum calcium, phosphorus or urinary calcium levels. Normalization of PTH was achieved in all patients with CKD 3 and in 8 patients with stage 4. One patient with CKD 4 needed an increase in paricalcitol dose.

Conclusion: Cholecalciferol can be used in correcting vitamin D deficiency in patients with all stages of CKD, however, its effectiveness in reducing PTH in stage 4 is limited. Selective analogs, such as paricalcitol, were well-tolerated and effectively decreased PTH levels.

Osteoporosis and Bone Diseases. 2018;21(2):12-22
Hereditary forms of primary hyperparathyroidism
Mamedova E.O., Mokrysheva N.G., Rozhinskaya L.Y.

Primary hyperparathyroidism (PHPT) is sporadic in the majority of cases. Hereditary forms of PHPT are rarer, however, they are of particular interest because they allow a deeper understanding of pathogenesis of parathyroid neoplasia. Hereditary forms of PHPT include multiple endocrine neoplasia type 1 (MEN-1), type 2A (MEN-2A), type 4 (MEN-4), hyperparathyroidism-jaw tumour syndrome (HPT-JT), variants of familial hypocalciuric hypercalcemia (FHH) and familial isolated hyperparathyroidism (FIHP). Mutations in the following genes cause the development of MEN-1, MEN-2A, MEN4, HPT-JT: MEN1, RET, CDKN1B, CDC73, respectively. Variants of FHH are caused by mutations in CASR, AP2S1, GNA11. Gene(s) responsible for the development of the majority of FIHP cases remain unknown.

Identification of hereditary forms of PHPT is important for patients and their first-degree relatives, as it allows defining the necessity of screening to reveal other components of the syndrome, in some cases determines the surgical approach to PHPT, and the risk of development of the disease in offsprings.

This article provides information on hereditary syndromes associated with PHPT and special features of PHPT in each syndrome.

Osteoporosis and Bone Diseases. 2018;21(2):23-29
Functional hypoparathyroidism: causes, pathogenesis, clinical significance in Bone tissue pathology
Nurullina G.M., Akhmadullina G.I., Maslova I.S.

Parathyroid hormone (PTH) regulates the maintenance of serum calcium concentration in strict limits through direct effects on bones and kidneys and indirectly due to the effect on the gastrointestinal tract. PTH also regulates phosphorus metabolism. Secondary hyperparathyroidism develops in response to a decreased serum calcium and vitamin D levels, leading to an increased bone resorption. However, the increase in parathyroid hormone above the reference values is not observed in all cases of vitamin D deficiency or hypocalcemia. Supressed or inadequately normal PTH in these conditions is referred to as functional hypoparathyroidism. Various theories have been suggested to explain the functional hypoparathyroidism: magnesium deficiency, intestinal calcistat, lower reference values for plasma PTH compared to current cut off interval, biological variations of vitamin D-binding protein. However, at present none of these theories are generally accepted. The clinical significance of functional hypoparathyroidism may be that vitamin D deficiency, hypocalcemia, and hypomagnesemia are associated with a risk of fracture, regardless PTH level.

Osteoporosis and Bone Diseases. 2018;21(2):30-35
Case report
Treatment of severe idiopathic hypoparathyroidism: a case report
Umiarova D.S., Grebennikova T.A., Tarbaeva N.V., Belaya Z.E.

Hypoparathyroidism is a rare disorder characterized by parathyroid hormone (PTH) insufficiency, the development of hypocalcemia and alteration of bone tissue remodeling.

The goal of treatment is to normalize the indicators of calcium-phosphorus metabolism and leveling of clinical manifestations. Standard treatment of hypoparathyroidism consists of oral calcium and active forms of vitamin D, in doses necessary to maintain calcium levels at the lower limit of the reference interval.

Nevertheless, treatment of the disease exerts certain difficulties in clinical practice. At the same time, compensation of the hypoparathyroidism is necessary to prevent ectopic calcification. Daily subcutaneous delivery of PTH (1–84) and PTH (1–34) has emerged as a promising therapeutic tool. However, its use should be restricted to patients insufficiently controlled with the standard treatment with active vitamin D and calcium.

We present a clinical case of idiopathic hypoparathyroidism with severe clinical presentation of hypocalcaemia and ectopic calcification. Idiopathic hypoparathyroidism is a consequence of autoimmune destruction of the parathyroid glands and is exhibited by excluding all known causes of hypoparathyroidism.

PTH (1–34) treatment allowed reducing the dose of calcium and vitamin D and achieving compensation of the disease.

Osteoporosis and Bone Diseases. 2018;21(2):36-40

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