Multifaceted skeletal effects of sevelamer carbonate in a secondary hyperparathyroidism model.

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM Endocrine Pub Date : 2025-02-07 DOI:10.1007/s12020-025-04180-4

Shivani Sharma, Saroj Kumar, Manendra Singh Tomar, Divya Chauhan, Sreyanko Sadhukhan, Chirag Kulkarni, Swati Rajput, Konica Porwal, Rajdeep Guha, Ashutosh Shrivastava, Jiaur R Gayen, Navin Kumar, Naibedya Chattopadhyay

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Abstract

Introduction: Hyperphosphatemia leads to abnormal mineralization of bones and soft tissues in patients with chronic kidney disease-induced secondary hyperparathyroidism (CKD-SHPT). Sevelamer lowers phosphate levels by binding to dietary phosphate in the gastrointestinal system, forming new bone and reducing the risk of renal osteodystrophy and fracture. However, the influence of sevelamer carbonate (SevC) on bone microarchitecture, material qualities, and mechanical behavior is unknown in CKD-SHPT conditions.

Material and methods: We utilized a rat model of CKD-induced hyperphosphatemia by feeding a 1.8% high-phosphate diet to 5/6 nephrectomized rats to test the effects of SevC on skeletal quality and strength, employing microCT, Fourier transform infrared spectroscopy (FTIR), 3-point bending, nanoindentation, and compression tests.

Results: SevC preserved mineral homeostasis and reduced PTH, and FGF-23 levels in CKD-SHPT rats. SevC mitigated the serum renal parameters, pyrophosphate levels, and indole acetic acid. In CKD-SHPT rats, SevC reduced hyperphosphatemia, improved the mineralization defect, and upregulated mineralization-promoting genes like ankyrin-1, ectonucleotide-pyrophosphatase/phosphodiesterase-1, tissue non-specific alkaline phosphatase, phosphate-regulating endopeptidase X-linked, dentin matrix protein-1, and matrix extracellular phosphoglycoprotein. In the cortical bones of CKD-SHPT rats, SevC increased cortical mass and thickness, decreased porosity by likely decreasing cortical bone remodeling induced by high PTH, and increased osteocyte preservation. SevC mitigated all of the alterations in the mineral and matrix composition of CKD-SHPT rats, including decreased collagen-maturity, mineral-to-matrix ratio, and increased carbonate substitution of hydroxyapatite crystals. SevC enhanced bone strength and mechanical behavior in CKD-SHPT rats at a macro (three-point bending) and nano (nanoindentation) scales.

Conclusion: These findings in CKD-SHPT rats suggest that SevC improves bone mechanical properties at various levels by decreasing serum pyrophosphate, empty lacunae, and enhancing renal clearance of indole acetic acid, organized mineral-matrix deposition, and osteocyte number by suppressing cortical remodeling.

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.