Vitamin D deficiency (NEJM clinical review)

Scope

Michael F. Holick (2007) provides a clinical-pathophysiology review of vitamin D metabolism, 25-hydroxyvitamin D as the circulating status marker, and why deficiency remains common despite fortification in some countries.

Sunlight / cutaneous synthesis (why this row sits on sunlight protocols)

• UVB (≈290–315 nm) photoconverts 7-dehydrocholesterol in skin to previtamin D₃, which thermally isomerizes to vitamin D₃.
• Latitude, season, time of day, skin pigmentation, aging, sunscreen use, and window glass all modulate effective dose—aligns with dose–response reviews such as Lewis et al. 2021 (lewis-2021-sunlight) and fracture-association work such as Kirsch et al. 2021 (kirsch-2021-sun).

Skeletal outcomes emphasized in the review narrative

• Children: deficiency states tied to rickets and growth impairment themes in classic deficiency descriptions.
• Adults: osteomalacia and osteoporosis / fracture-risk physiology when mineralization and remodeling are impaired by chronic insufficiency.

Evidence hygiene

• This is a narrative review, not a pooled trial effect size for fractures—pair with Kirsch (prospective association) and supplementation / guideline syntheses when readers need intervention numbers.
• Non-skeletal disease threads in the same review are hypothesis / association heavy in the broader literature—do not substitute this citation for disease-specific RCTs.