Biochemical Markers of Calcium and Bone Metabolism during and after Lactation in Ugandan Women with HIV on Universal Maternal Antiretroviral Therapy

IF 5.1 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Bone and Mineral Research Pub Date : 2023-06-12 DOI:10.1002/jbmr.4866

Florence Nabwire, Matthew M. Hamill, Mary Glenn Fowler, Josaphat Byamugisha, Adeodata Kekitiinwa, Ann Prentice

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Abstract

We reported accentuated lactational decreases in areal bone mineral density and only partial skeletal recovery after lactation in Ugandan women with HIV (WWH) initiated on tenofovir disoproxil fumarate-based antiretroviral therapy (TDF-based ART) during pregnancy compared to women without HIV (REF). WWH also had higher breast milk calcium in the first months of lactation. To investigate the mechanisms, we measured bone turnover markers (bone resorption: C-terminal telopeptide [CTX]; bone formation: procollagen type 1 N-terminal propeptide [P1NP], bone-specific and total alkaline phosphatase [BALP, TALP]), hormones (parathyroid hormone [PTH], intact fibroblast growth factor 23 [FGF23], 1,25-dihydroxyvitamin D [1,25(OH)₂D]), vitamin D status (25-hydroxyvitamin D [25OHD]), and indices of mineral metabolism and renal function. Blood and urine samples collected at 36 weeks of gestation, 14 and 26 weeks of lactation, and 3–6 months after lactation were analyzed. Mean 25OHD was >50 nmol/L throughout. Both groups experienced similar biochemical changes during pregnancy and lactation to women in other settings, but within these patterns, the two groups differed significantly. Notably, WWH had higher PTH (+31%) and lower 1,25(OH)₂D (−9%) and TmP/GFR (−9%) throughout, lower P1NP (−27%) and plasma phosphate (−10%) in pregnancy, higher CTX (+15%) and BALP (+19%), and lower eGFR (−4%) during and after lactation. P1NP/CTX ratio was lower in WWH than REF in pregnancy (−21%), less so in lactation (−15%), and similar after lactation. Additionally, WWH had lower plasma calcium (−5%), lower FGF23 (−16%) and fasting urinary calcium (−34%) at one or both lactation timepoints, and higher fasting urinary phosphate (+22%) at 26 weeks of lactation and after lactation. These differences resemble reported TDF effects, especially raised PTH, increased bone resorption, decreased bone formation, and decreased renal function, and may explain the observed differences in bone mineral density and breast milk calcium. Further studies are needed to determine whether HIV and TDF-based ART have long-term consequences for maternal bone health and offspring growth. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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通用母体抗逆转录病毒治疗的乌干达HIV感染妇女哺乳期和哺乳后钙和骨代谢的生化标志物

我们报道，与未感染艾滋病毒的妇女相比，乌干达感染艾滋病毒（WWH）的妇女在怀孕期间接受富马酸替诺福韦二普罗酯抗逆转录病毒治疗（TDF抗逆转录病毒疗法），其区域骨密度在哺乳期显著下降，哺乳后仅部分骨骼恢复（REF）。WWH在泌乳的前几个月也有较高的母乳钙。为了研究其机制，我们测量了骨转换标志物（骨吸收：C末端末端肽[CTX]；骨形成：1型前胶原 N-末端前肽[P1NP]、骨特异性和总碱性磷酸酶[BALP，TALP]）、激素（甲状旁腺激素[PTH]、完整成纤维细胞生长因子23[FGF23]、1,25-二羟基维生素D[1,25（OH）2D]）、维生素D状态（25-羟基维生素D[25OHD]）以及矿物质代谢和肾功能指标。36时采集的血液和尿液样本妊娠14周和26周哺乳周，以及3-6周对泌乳后的月数进行分析。平均25OHD为>；50 nmol/L。两组在怀孕和哺乳期间都经历了与其他环境中的女性相似的生化变化，但在这些模式下，两组差异显著。值得注意的是，WWH在整个过程中具有较高的PTH（+31%）和较低的1,25（OH）2D（−9%）和TmP/GFR（−9%。妊娠期WWH的P1NP/CTX比率低于REF（−21%），哺乳期较低（−15%），哺乳后相似。此外，在一个或两个哺乳时间点，WWH的血浆钙（−5%）较低，FGF23（−16%）和空腹尿钙（−34%）较低哺乳周和哺乳后。这些差异类似于报道的TDF效应，特别是PTH升高、骨吸收增加、骨形成减少和肾功能下降，并可能解释观察到的骨密度和母乳钙的差异。需要进一步的研究来确定基于HIV和TDF的ART是否对母体骨骼健康和后代生长有长期影响。©2023作者。由Wiley Periodicals LLC代表美国骨与矿物研究学会（ASBMR）出版的《骨与矿产研究杂志》。

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来源期刊

Journal of Bone and Mineral Research 医学-内分泌学与代谢

CiteScore

11.30

自引率

6.50%

发文量

257

审稿时长

2 months

期刊介绍： The Journal of Bone and Mineral Research (JBMR) publishes highly impactful original manuscripts, reviews, and special articles on basic, translational and clinical investigations relevant to the musculoskeletal system and mineral metabolism. Specifically, the journal is interested in original research on the biology and physiology of skeletal tissues, interdisciplinary research spanning the musculoskeletal and other systems, including but not limited to immunology, hematology, energy metabolism, cancer biology, and neurology, and systems biology topics using large scale “-omics” approaches. The journal welcomes clinical research on the pathophysiology, treatment and prevention of osteoporosis and fractures, as well as sarcopenia, disorders of bone and mineral metabolism, and rare or genetically determined bone diseases.