{"doi":"10.1681/asn.0000000848","title":"The Use of Time-Lapse High-Resolution Peripheral Quantitative Computed Tomography for Noninvasive Bone Turnover and Bone Quality Assessment in CKD","abstract":"CKD is a global health problem affecting approximately 10% of the population. CKD-associated osteoporosis, as defined by the recent Kidney Disease Improving Global Outcomes guidelines, is a complex and multifactorial skeletal disorder.1 Patients with CKD-associated osteoporosis exhibit an advanced aging skeletal phenotype; they have two-fold to six-fold higher hip fracture risk compared with age-matched and sex-matched individuals without CKD, and these fractures are associated with four-fold to six-fold higher mortality.2 CKD-associated osteoporosis is largely characterized by abnormalities in bone mass, mineralization, and turnover. Histologically, patients with CKD often present with extreme high or low turnover. Although both subtypes may result in net bone loss and increased bone fragility, they are managed with different bone-targeted therapeutic strategies. Specifically, patients with low turnover may benefit from strategies to increase turnover, such as decreasing vitamin D and calcium intake in the setting of parathyroid hormone oversuppression or initiating an anabolic agent (e.g., teriparatide). By contrast, patients with high turnover may benefit from strategies to suppress turnover, such as lowering parathyroid hormone levels by initiating activated vitamin D, calcimimetics, dietary phosphate control, phosphate binders, or antiresorptive treatments (e.g., bisphosphonates).1 In addition, patients with CKD can experience changes in turnover with disease progression or concurrent treatment. Thus, knowledge of turnover before and during treatment may be critical for optimizing clinical management of CKD-associated osteoporosis by monitoring treatment efficacy and informing therapeutic strategies. An important roadblock to the management of CKD-associated osteoporosis is the inability to obtain accurate turnover assessments. The gold standard turnover assessment is tetracycline double-labeled iliac crest bone biopsy with quantitative histomorphometry, which is the only technique that quantitatively and mechanistically assesses bone tissue–level and cellular-level features that may be impaired in CKD. However, bone biopsy with histomorphometry is invasive, expensive, and requires highly specialized expertise. This procedure is available at very few centers worldwide and is rarely performed repeatedly in the same individual in clinical practice to monitor response to treatment. Consequently, despite broad recognition of its clinical value among nephrologists and ongoing efforts to promote its wider implementation, the procedure is rarely performed clinically for managing CKD-associated osteoporosis.3 As such, many patients with CKD receive either no treatment or treatment that is not optimized for their individual turnover subtype. Noninvasive assessments offer alternative approaches for bone turnover evaluation. Circulating bone turnover markers are well-established in the general population4; however, their use in CKD is controversial. Some bone turnover markers are cleared by the kidney and accumulate with declining kidney function, independent of turnover status. Although Kidney Disease Improving Global Outcomes, the International Federation of Clinical Chemistry and Laboratory Medicine, and the International Osteoporosis Foundation recommend a systematic incorporation of non–kidney-cleared bone turnover markers in CKD, their clinical implementation and effectiveness on predicting patient-relevant outcomes, including bone loss and fracture, remain unestablished.1,4 Furthermore, studies to date have shown low positive predictive values, making their interpretation to guide patient-specific clinical decision making challenging. 18F-sodium fluoride positron emission tomography is an advanced imaging modality that has shown promise in classifying bone turnover subtypes5; however, its clinical application is limited by high radiation exposure and the need for specialized expertise. Similarly, 44/42Ca ratio is an emerging ","journal":"Journal of the American Society of Nephrology","year":2025,"id":528631,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1374205,"name":"I.W. Yu","orcid":null,"position":1,"is_corresponding":false},{"id":339671,"name":"Isidro B. Salusky","orcid":"0000-0001-8052-416X","position":2,"is_corresponding":false},{"id":240852,"name":"Thomas L. Nickolas","orcid":"0000-0001-8870-1896","position":3,"is_corresponding":false},{"id":261907,"name":"Joachim H. Ix","orcid":"0000-0002-8084-9869","position":4,"is_corresponding":false},{"id":445233,"name":"Galateia J. Kazakia","orcid":"0000-0002-7327-6425","position":5,"is_corresponding":false},{"id":1287501,"name":"Minhao Zhou","orcid":"0000-0001-8084-3638","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-19T02:50:48.492873Z","pmid":"40779346","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}