Table 1 Changes in serum sclerostin levels in various physiologic and pathological conditions

Physiologic states

 Age: adults and elderly

Increase with age

Serum sclerostin levels increase with age, but bone marrow sclerostin mRNA is not increased in older patients.

 Gender

Higher in men

Likely due to higher bone mass (osteocyte number); lower in premenopausal women because of estrogen effect.

 Menopause

Higher after menopause

Lack of inhibitory effect of estrogen or decreased bone formation leading to low osteocyte number.

 Malnutrition

Blunts sclerostin changes

In patients with anorexia nervosa, sclerostin does not decrease with estrogen therapy.

Hormones

 Parathyroid hormone

Decrease

Direct effect on osteoblast, osteocyte number, and on Wnt signaling.

 Vitamin D

Increase

Limited data; one study each in normal and dialysis patients; confounding by PTH is likely.

 Estrogen

Decrease

Direct effect of estrogen and possibly SERMs on osteoblast/osteocyte number and function.

 Androgen

Data unclear

Increased in prostate cancer patients and during androgen deprivation therapy.

 Leptin

Increased

Sclerostin levels were higher in obese patient and correlated with leptin and PTH levels.

 Growth hormone/IGF

Data unclear

IGF is obligatory to the anabolic action of PTH; may be for osteocyte function and sclerostin as well.

Pathologic conditions

 Bone and mineral disorders

  Hyperparathyroidism (Primary)

Decrease

Lower levels compared with controls in untreated patients and normalize after parathyroidectomy.

  Paget’s disease of bone

Increased

Sclerostin did not correlate with P1NP or CTX.

  Glucocorticoid-induced osteoporosis

Early increase/later decline

Varies with timing of the study with reference to steroid use.

  Cushing’s disease

Decreased

Increased after treatment, suggesting suppressive effects on osteocyte and osteoblast function.

 Osteoporosis treatment effects

  Bisphosphonates and denosumab

Increase

Results may vary due to timing of data collection after denosumab or zolendronic acid administration.

  Teriparatide and strontium ranelate

Decreased

Compensatory increase in Dkk1 levels may limit continued anabolic action.

  Estrogen and raloxifene

Decreased

Suggesting estrogen and estrogen effect of raloxifene may modulate osteocyte and osteoblast function.

 Systemic disorders

  Diabetes mellitus type 1

Slight increase

Age-related increase maintained, but sclerostin response to PTH is blunted.

  Diabetes mellitus type 2

Increased

Age-related increase is absent, sclerostin response to PTH is impaired, and pioglitazone therapy increases sclerostin levels by 11 %.

  Chronic kidney disease

Increased

Sclerostin excretion increases with declining renal function with negative correlation with GFR.

  Kidney disease

Increased

Sclerostin levels increase despite increased PTH and increased excretion of sclerostin in renal failure.