Complex Regional Pain Syndrome 14X more likely if low Vitamin D

Association Between Vitamin D Deficiency and the Development of Complex Regional Pain Syndrome: A Retrospective Case-Control Study

Acta Orthop Belg. 2025 Sep;91(3):341-346. doi: 10.52628/91.3.13185n PDF behind paywall

G Demir Karakiliç, S Gümrük Aslan, F Surel

Vitamin D deficiency has been suggested as a potential contributing factor in the development of Complex Regional Pain Syndrome (CRPS). This study aimed to investigate the association between serum vitamin D levels and CRPS using a retrospective case-control design. The study included 306 individuals divided into three groups: CRPS patients (n=102), fracture patients without CRPS (n=102), and healthy controls (n=102). Only patients whose vitamin D levels were measured during June, July, or August were included to minimize seasonal variation. Mean serum vitamin D levels were significantly lower in the CRPS group (10.2 ng/mL) compared to the fracture group (20.4 ng/mL) and control group (26.3 ng/mL) (p<0.001). The prevalence of vitamin D deficiency was highest in the CRPS group, followed by the fracture group, and lowest in the control group.

Binary logistic regression analysis confirmed that vitamin D deficiency was independently associated with the presence of CRPS (OR: 14.57, 95% CI: 5.48-38.73, p<0.001), while age and sex were not significant predictors. No significant correlation was observed between serum vitamin D levels and other biochemical parameters.

Vitamin D deficiency was more frequently observed in patients with CRPS than in fracture patients and healthy controls. These findings suggest an association between low vitamin D levels and the presence of CRPS. Further prospective studies are warranted.

Claude AI on CRPS - March 2026

Complex Regional Pain Syndrome (CRPS) is a chronic pain condition characterized by severe, persistent pain that is disproportionate to the original injury or tissue damage that triggered it. It most commonly affects the arms, legs, hands, or feet.

Two Types

CRPS-I (formerly called Reflex Sympathetic Dystrophy): No confirmed nerve damage; often follows a minor injury like a sprain or fracture.
CRPS-II (formerly called Causalgia): Associated with a confirmed nerve injury.

Key Symptoms

Intense burning or throbbing pain, often far exceeding what the initial injury would explain
Extreme sensitivity to touch or cold (allodynia — pain from stimuli that shouldn't cause pain)
Swelling and changes in skin temperature (alternating hot and cold)
Skin color changes (blotchy, purple, pale, or red)
Changes in skin texture (shiny, thin, or sweaty)
Changes in hair and nail growth patterns
Stiffness, swelling, and reduced range of motion in affected joints
Muscle weakness or atrophy in severe cases

Causes & Triggers

The exact mechanism isn't fully understood, but CRPS is thought to involve an abnormal response of the nervous system — both peripheral and central — often following trauma such as fractures, surgery, stroke, or even minor injuries. In some cases, no clear trigger is identified.

Who Gets It

It can affect anyone, but is more common in women, typically between ages 40–70. Children and adolescents can also develop it.

Treatment

There is no cure, but treatment aims to reduce pain and restore function. Approaches include:

Physical and occupational therapy
Pain medications (NSAIDs, anticonvulsants like gabapentin, antidepressants)
Corticosteroids
Nerve blocks (sympathetic nerve blocks)
Spinal cord stimulation
Psychological support (as chronic pain takes a significant mental health toll)
Ketamine infusions (in refractory cases)

Prognosis

Outcomes vary widely. Some people recover with early, aggressive treatment. Others develop a chronic, debilitating condition. Early diagnosis and intervention significantly improve outcomes.

It's considered one of the more poorly understood and difficult-to-treat chronic pa in conditions in medicine.

CRPS is underdiagnosed, mainly women, 2-5 years to diagnose, very painful - Claudie AI March 2026

It's surprisingly common, though often underdiagnosed. Here are the key numbers:

Incidence (new cases per year) - Estimated 5–26 cases per 100,000 people per year, depending on the study and country - A large Dutch study (one of the best epidemiological studies on CRPS) found about 26 per 100,000 per year - U.S. estimates tend toward the lower end, around 5–7 per 100,000

Prevalence (total people living with it) - Roughly 200,000 Americans are estimated to have CRPS at any given time - Some estimates go higher, up to 5 million, partly because mild cases often go unrecognized

Demographics - Women are affected 3–4 times more often than men - Peak onset is around age 40–70, but it occurs at all ages - The upper limb (arm/hand) is more commonly affected than the lower limb - Fractures are the most common trigger (~45% of cases), followed by sprains and surgery

Why You May Not Have Heard of It - It's frequently misdiagnosed — patients are sometimes told their pain is psychosomatic before getting a correct diagnosis - Average time to diagnosis can be 2–5 years - It doesn't have the public profile of conditions like fibromyalgia or MS, despite comparable or greater severity - Many clinicians receive little training on it

Severity Context On pain scales, CRPS consistently ranks among the most painful conditions known to medicine — often rated above cancer pain, amputation, and childbirth on the McGill Pain Index. That combination of severity and relative obscurity makes it a particularly difficult condition for patients to navigate.