Why can Vitamin D deficiency cause joint pain and swelling?

Vitamin D deficiency causes your immune system to produce an inflammatory type of white (T) blood cells that may lead to autoimmune diseases like rheumatoid arthritis, which causes joint pain and swelling. 40% of Americans have Vitamin D deficiency due to low sunlight exposure.

Vitamin D Recommended Daily Dose

The recommended daily dose of vitamin D is:

  • 400 IU for ages less than 1 year old
  • 600 IU for ages 1 to 70 years
  • 800 IU for ages over 70 years

The video below shows that vitamin D deficiency is common in people with rheumatoid arthritis (RA), and may be linked to musculoskeletal pain.

Bone pain after taking Vitamin D?

Taking too much vitamin D3 or D2 (>10,000 IU/day) causes hypercalcemia (excess calcium in blood) and hypercalciuria (excess calcium in urine). Symptoms include: bone pain, weakness or fractures.

Ingestion of vitamin D3 or vitamin D2 higher than 10 000 IU/d in an adults (and lower amounts in children) could cause vitamin D intoxication, especially hypercalciuria and/or hypercalcemia because the concentration in blood rises steeply at intakes >10,000 IU/d. 

Vitamin D-associated hypercalcemia occurs only when extremely large doses of vitamin D (often several hundred-fold the recommended intake) are ingested.

Symptoms of vitamin D toxicity, result of hypercalcemia and hypercalciuria include:

Psychiatric symptoms such as:

  • lethargy
  • confusion
  • irritability
  • depression
  • hallucination
  • in extreme cases, stupor, and coma

Gastrointestinal symptoms such as:

  • anorexia
  • nausea
  • vomiting
  • constipation

Cardiovascular manifestations such as ectopy (disturbance of the cardiac rhythm)

Renal symptoms such as:

  • polyuria (urine output of more than 3 liters per day)
  • renal colic from the passage of renal stones
Very high magnification micrograph of bone in hypercalcemia. Author: Wikimedia Commons contributors.

Unrecognised severe vitamin D deficiency case

A 53 year old woman of Pakistani origin underwent mastectomy for carcinoma of the right breast with radiotherapy and tamoxifen treatment.

Over the next two years she presented at her follow-up appointments with musculoskeletal pains, including pain in the right arm, loin, right posterior chest with bony tenderness and whole body discomfort. A chest x ray showed a diagnosis of metastatic bone disease.

Over the next six months her pains worsened, and areas of tenderness in the arms, legs, ribs, and left sacroiliac joint were poorly controlled. A repeat bone scan showed no change. A poor prognosis was given and combination chemotherapy was planned, but first she took a six week summer trip to Pakistan to visit family.

On her return to the United Kingdom, her symptoms had completely resolved. A whole body computed tomography scan showed a pelvic stress fracture but no evidence of metastasis. Chemotherapy was delayed.

Study Information

  • Title: Relationship between unexplained arthralgia and vitamin D deficiency: a case control study.

Subject Information

  • Number of Subjects: 167 patients with low vitamin D levels and a 283 control group with normal vitamin D levels.
  • Mean age: 38 years for patient group and 42.6 years for control group.
  • Health Status: low vitamin D levels.

Method used

Patients with arthralgia not related to a definite medical condition were selected among subjects presented to a rheumatology clinic. Serum 25-hydroxyvitamin D (25-OHD) was measured by ELISA method and levels less than 20 ng/ml were considered as deficient levels. 25-OHD levels in the blood and proportion of 25-OHD deficiency was compared in patients versus the control group.


In patients mean serum 25-OHD was lower and proportion of deficiency was higher. Serum 25-OHD deficiency was associated with 3.01 times increased risk of arthralgia. After adjusment for age and sex, the risk of arthralgia remained significant. The odds of arthralgia decreased with increasing 25-OHD levels.


These findings indicate significant association of vitamin D deficiency causing joint pain. Regarding vitamin D deficiency as an environmental factor for development or progression of rheumatic diseases, this study justifies identification and correction of vitamin D deficiency in patients with joint pain.

Vitamin D deficiency and insufficiency may contribute to musculoskeletal symptoms and bone loss observed in women taking aromatase inhibitors (AIs). This study was conducted to determine the prevalence of suboptimal vitamin D levels in women initiating adjuvant letrozole for breast cancer and to determine whether supplementation with 50,000 IU of vitamin D3 weekly could reduce musculoskeletal symptoms and fatigue in women who have suboptimal vitamin D levels.

Study 1

  • Title: Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer.
  • Length: 16 weeks.

Subject Information

  • Number of Subjects: 60.
  • Gender: female.
  • Health Status: breast cancer.

Method used

Baseline 25OHD levels were obtained, and women completed symptom questionnaires. They were then started on letrozole, along with standard dose calcium and vitamin D.

Four weeks later, women with baseline 25OHD levels </=40 ng/ml started additional vitamin D3 supplementation at 50,000 IU per week for 12 weeks. 25OHD levels were re-assessed at 4, 10, and 16 weeks; the questionnaires were repeated at weeks 4 and 16. At baseline, 63% of women exhibited vitamin D deficiency (<20 ng/ml) or insufficiency (20-31 ng/ml).


25OHD levels >40 ng/ml were achieved in all 42 subjects who received 12 weeks of supplementation with 50,000 IU vitamin D3 weekly, with no adverse effects.

After 16 weeks of letrozole, more women with 25OHD levels >66 ng/ml (median level) reported no disability from joint pain than did women with levels <66 ng/ml. Vitamin D deficiency and insufficiency are prevalent in post-menopausal women initiating adjuvant AI.


Vitamin D3 supplementation with 50,000 IU per week is safe, significantly increases 25OHD levels, and may reduce disability from AI-induced arthralgias.

Aromatase inhibitor (AI)-associated arthralgia limits adherence to therapy in breast cancer. The pathophysiology may involve vitamin D status. We wished to establish the optimal concentration of 25(OH)D that prevents or minimizes arthralgia.

Study 2

  • Title: Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study.
  • Length: 12 weeks.

Subject Information

  • Number of Subjects: 290.
  • Gender: female.
  • Health Status: breast cancer.

Method used

We used a prospective cohort of 290 women starting AI in whom baseline vitamin D was measured. All received daily vitamin D(3) (800 IU) with calcium. Women with baseline 25(OH)D concentration <30 ng/ml also received 16,000 IU of D(3) orally every 2 weeks.

We analysed the association between vitamin D concentrations at 3 months and pain adjusting for age, BMI, season when the sample was drawn, aromatase inhibitor (exemestane vs. letrozole/anastrozole), prior previous fracture. 90% of women had a 25(OH)D <30 ng/ml at baseline.


After supplementation (daily 800 IU and additional 16,000 IU every 2 weeks), 50% of them still failed to reach adequate concentrations at 3 months. In the whole cohort, there was an increase in joint pain and the increase was significantly attenuated in those that reached concentrations of 25(OH)D of ≥40 ng/ml, with a lower risk of incident arthralgia.


A target concentration of 40 ng/ml 25OHD may prevent development of AI arthralgia but higher loading doses are required to attain this level in women with deficiency at baseline.

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This article makes use of information from the U.S. National Library of Medicine under the terms of the Creative Commons Attribution 4.0 International License.

  1. Heidari B, Heidari P, Tilaki KH. Relationship between unexplained arthralgia and vitamin D deficiency: a case control study. Acta Med Iran. 2014;52(5):400-405.
  2. Khan QJ, Reddy PS, Kimler BF, et al. Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer. Breast Cancer Res Treat. 2010;119(1):111-118. doi:10.1007/s10549-009-0495-x
  3. Prieto-Alhambra D, Javaid MK, Servitja S, et al. Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study. Breast Cancer Res Treat. 2011;125(3):869-878. doi:10.1007/s10549-010-1075-9
  4. Tebben PJ, Singh RJ, Kumar R. Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment. Endocr Rev. 2016;37(5):521-547. doi:10.1210/er.2016-1070
  5. Sievenpiper JL, McIntyre EA, Verrill M, Quinton R, Pearce SH. Unrecognised severe vitamin D deficiency. BMJ. 2008;336(7657):1371-1374. doi:10.1136/bmj.39555.820394.BE
Why can Vitamin D deficiency cause joint pain and swelling?
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