Rethinking Vitamin D Deficiency: Controversies and Practical Guidance for Clinical Management

Abstract

Vitamin D (VD), due to its hormonal action, plays a crucial role in calcium homeostasis and bone metabolism, and its deficiency has been associated with musculoskeletal disorders such as osteoporosis, fractures, and osteomalacia, as well as a growing attention of chronic conditions and certain cancers. Despite its physiological relevance and widespread prevalence, particularly among older individuals, patients with chronic diseases, institutionalized populations and pregnant or lactating women, clinical approaches to diagnosing and managing vitamin D deficiency (VDD) remain heterogeneous across guidelines and healthcare settings. This reflects a lack of consensus regarding the benefits and limitations of universal versus selective screening, the definition of adequate serum concentrations, and the clinical indications for supplementation across different patient profiles. This narrative review explores key controversies in the clinical management of VDD, including current perspectives on screening strategies and target populations, indications for empirical supplementation, criteria for biochemical monitoring, and therapeutic goals in bone-related outcomes. In particular, the review discusses the rationale for adopting a 30 ng/mL (75 nmol/L) threshold for adequate serum 25(OH) concentrations in skeletal health, the role of vitamin D and calcium in osteoporosis treatment, and the pharmacological advantages of cholecalciferol compared to other vitamin D compounds. Through a synthesis of available evidence and expert consensus, the review aims to support clinical decision-making in the prevention and treatment of VDD and to identify areas that require further clarification or research. This review aims to support evidence-based clinical decision-making.