Baseline Vitamin D & Calcium Balance
Normal vitamin D keeps calcium absorption and PTH steady.
- 30–50: Normal 25-OH-D (ng/mL sufficient)
- ~30%: Normal Ca²⁺ absorption (of dietary intake)
- 10–65: Normal PTH (pg/mL reference range)
- balanced: Bone remodeling (formation = resorption)
Vitamin D activation pathway
Skin, diet, and liver/kidney convert vitamin D into active calcitriol.
Intestinal calcium absorption
Calcitriol upregulates gut transporters that absorb dietary calcium.
Parathyroid set point
Calcium-sensing receptors keep PTH secretion low when calcium is adequate.
Vitamin D Deficiency Develops
Low sun exposure, diet, or malabsorption drop calcitriol output.
- <20: Deficient 25-OH-D (ng/mL threshold)
- ~1 B: Global prevalence (people affected)
- 3+: Main causes (sun, diet, malabsorption)
- weeks: Onset timeline (to become measurable)
Falling calcitriol
Less substrate and enzyme activity reduce active hormone levels.
Absorption transporters idle
Gut calcium channels are no longer upregulated as before.
Still asymptomatic
Blood calcium has not yet fallen — deficiency is silent.
Serum Calcium Begins To Drop
Reduced intestinal absorption outpaces dietary calcium intake.
- 8.5–10.5: Normal serum Ca²⁺ (mg/dL)
- ~10–15%: Absorption falls to (in deficiency)
- blood: Detection method (panel + 25-OH-D)
- days: Compensation lag (before PTH responds)
Absorption shortfall
Less calcium crosses the gut wall into the bloodstream.
Calcium sensing
Parathyroid cells detect the small decline in ionized calcium.
Compensation begins
Falling calcium is the trigger for the PTH response.
Secondary Hyperparathyroidism
PTH rises to pull calcium from bone and kidney.
- >65: Elevated PTH (pg/mL secondary rise)
- ↑: Bone resorption (osteoclast activation)
- ↑: Renal reabsorption (less calcium lost in urine)
- ~normal: Serum calcium (restored by compensation)
PTH surge
Parathyroid glands secrete more hormone to defend blood calcium.
Bone resorption activated
PTH signals osteoclasts to release calcium from bone matrix.
Kidney conserves calcium
Renal tubules reabsorb more calcium, less is excreted.
Chronic Bone Demineralization
Ongoing compensation slowly drains bone mineral reserves.
- adults: Osteomalacia (softened bone matrix)
- children: Rickets (growth plate deformity)
- progressive: BMD decline (over months to years)
- normal Ca²⁺: Masked risk (hides bone loss)
Hidden cost of compensation
Bone is sacrificed to keep blood calcium near normal.
Progressive thinning
Chronic resorption exceeds bone formation over time.
Clinical consequence
Fracture risk and bone pain rise as density declines.