What clinical manifestations should be expected in a patient with a deficient serum 25‑hydroxyvitamin D (25‑OH‑D) level of 21 ng/mL?

Clinical Manifestations of Vitamin D Deficiency at 21 ng/mL

A serum 25-hydroxyvitamin D level of 21 ng/mL represents vitamin D insufficiency (20–30 ng/mL range), and at this level you should anticipate musculoskeletal symptoms including symmetric low back pain, proximal muscle weakness, muscle aches, and throbbing bone pain that is elicited by pressure over the sternum or tibia. 1

Primary Musculoskeletal Symptoms

The most characteristic clinical manifestations at this level include:

• Symmetric low back pain that is often diffuse and difficult to localize 1
• Proximal muscle weakness, particularly affecting the hip flexors and shoulder girdle, which may manifest as difficulty rising from a chair or climbing stairs 1
• Generalized muscle aches (myalgias) that patients often describe as a deep, aching discomfort 1
• Bone pain with a throbbing quality that is reproducible when pressure is applied to the sternum or anterior tibia 1

Metabolic Consequences

At 21 ng/mL, the patient is at increased risk for:

• Secondary hyperparathyroidism, as PTH begins to rise when 25(OH)D falls below 30 ng/mL, with some studies showing elevation starting between 30–78 nmol/L (12–31 ng/mL) depending on calcium intake 2
• Increased bone turnover markers and accelerated bone loss, raising fracture risk even before overt deficiency develops 3
• Reduced anti-fracture efficacy, since levels ≥30 ng/mL are required for optimal fracture prevention, and this patient falls short of that threshold 4

Functional Impairments

Patients with insufficiency in this range commonly experience:

• Increased fall risk, as anti-fall efficacy requires achieved levels of at least 24 ng/mL, and this patient is only marginally above that threshold 4
• Functional limitations in daily activities due to the combination of muscle weakness and bone pain 3

Important Clinical Context

The severity of symptoms varies considerably between individuals. Some patients with a level of 21 ng/mL may be entirely asymptomatic, while others experience significant musculoskeletal complaints 1. The presence and intensity of symptoms depend on:

• Duration of insufficiency—chronic insufficiency is more likely to produce symptoms than acute drops 4
• Calcium intake—low dietary calcium (below 1000–1200 mg/day) exacerbates the metabolic consequences of vitamin D insufficiency by further stimulating PTH secretion 2
• Body composition—obesity sequesters vitamin D in adipose tissue, potentially worsening the functional deficit despite measurable serum levels 3
• Age—elderly patients (≥65 years) are more vulnerable to the musculoskeletal effects of insufficiency 4

Common Diagnostic Pitfall

Do not dismiss mild symptoms or attribute them to other causes without addressing the vitamin D insufficiency. Even "borderline" levels like 21 ng/mL are associated with measurable increases in fracture risk, falls, and secondary hyperparathyroidism 3, 2. The goal of treatment is to normalize levels to ≥30 ng/mL to relieve symptoms and reduce these risks 1.

What This Patient Does NOT Typically Experience

At 21 ng/mL (insufficiency rather than severe deficiency), you would not expect:

• Severe osteomalacia or rickets, which require levels typically below 10–12 ng/mL 4
• Hypocalcemia, as calcium levels usually remain normal until deficiency is more profound 4
• Pathological fractures in the absence of other risk factors, though fracture risk is elevated compared to sufficient levels 4