Rickets is a disorder of bone mineralization in growing children, where bones cannot properly incorporate calcium and phosphate, leading to soft and weakened skeletal structures. It is most often associated with a deficiency of Vitamin D, which helps the body absorb these minerals. Vitamin D Resistant Rickets (VDRR) is a rare and more severe group of disorders that fundamentally differs from this common nutritional cause. The term “resistant” is used because the condition fails to respond to the standard doses of Vitamin D supplementation used to treat deficiency. This signals a problem not with the intake of the vitamin, but with the body’s ability to process or utilize it effectively.
Defining Vitamin D Resistant Rickets
VDRR is characterized by a fundamental defect in the body’s mineral homeostasis, particularly involving phosphate and calcium. It involves a malfunction in the hormonal pathways that regulate bone growth, rather than a lack of Vitamin D. In many cases, the body has sufficient Vitamin D, but the tissues that need to respond to its active form are impaired. This internal resistance prevents necessary mineralization from occurring at the growth plates, where new bone is formed.
VDRR is often referred to as hypophosphatemic rickets because it is primarily a disorder of phosphate wasting and impaired mineral balance. Phosphate is a major component of the bone mineral matrix. Sustained low levels of phosphate in the blood (hypophosphatemia) lead directly to soft bones that cannot support the body’s weight, resulting in the skeletal deformities characteristic of rickets.
The Underlying Genetic Cause
VDRR is overwhelmingly a congenital condition, meaning it is present from birth. The most common form is X-linked hypophosphatemia (XLH), caused by a mutation on the PHEX gene located on the X chromosome. This mutation leads to the overproduction of fibroblast growth factor 23 (FGF-23), which acts as a “phosphatonin.” FGF-23 signals the kidneys to excrete phosphate and reduces the production of active Vitamin D, resulting in chronic phosphate loss.
Hereditary Vitamin D-Resistant Rickets (HVDRR)
A rarer form is Hereditary Vitamin D-Resistant Rickets (HVDRR), also known as Vitamin D-dependent rickets Type II. This involves a specific defect in the Vitamin D receptor (VDR). VDR gene mutations prevent the active form of Vitamin D, calcitriol, from binding to its receptor inside cells. Because the receptor cannot signal properly, the body fails to absorb calcium and phosphate from the intestine. HVDRR is typically inherited in an autosomal recessive pattern, requiring both parents to carry a copy of the mutated gene.
Recognizing Clinical Signs and Diagnosis
The observable symptoms of VDRR typically become apparent in infancy or early childhood, particularly when a child begins to bear weight. Skeletal deformities are common, including the bowing of the legs (genu varum) or knock-knees (genu valgum), which result from soft bones bending under pressure. Children often experience bone pain, a waddling gait, delayed growth, and short stature. Dental abnormalities, such as abscesses and delayed tooth eruption, are also frequently observed due to the mineral defect.
Diagnosis is confirmed through imaging and specialized blood tests. X-rays reveal characteristic changes, including widened and frayed growth plates in the long bones, indicating defective mineralization. Biochemical analysis of the blood is necessary for differentiating VDRR types from nutritional rickets. All forms of VDRR generally exhibit very high levels of the bone enzyme alkaline phosphatase (ALP), which is a marker of increased, but ineffective, bone turnover.
Differentiating VDRR Types
In HVDRR caused by a VDR defect, blood tests show low calcium and phosphate levels, but the active Vitamin D (calcitriol) level is paradoxically very high as the body attempts to compensate for the receptor resistance. By contrast, in XLH, the blood profile typically shows low phosphate levels with near-normal calcium and often normal to mildly decreased active Vitamin D levels. These specific mineral and hormonal patterns guide the medical team toward the correct genetic diagnosis and appropriate treatment strategy.
Specialized Treatment and Management
Standard treatment for nutritional rickets—simple Vitamin D supplements—is ineffective for VDRR. Specialized therapeutic strategies focus on correcting the mineral imbalance and bypassing the mechanisms of resistance. For most forms of VDRR, including XLH, the primary regimen involves the lifelong administration of oral phosphate supplements several times a day to maintain adequate blood levels. This is combined with active Vitamin D analogs, such as calcitriol, to help the body absorb the necessary minerals.
For severe cases of HVDRR, where the Vitamin D receptor is highly resistant, oral treatment may not be sufficient. Patients may require intravenous calcium infusions to bypass the intestinal absorption defect entirely. The goal of this intensive treatment is to promote the healing of rickets, prevent further bone deformities, and support normal growth. Management requires a dedicated, multidisciplinary medical team, including pediatric endocrinologists, nephrologists, and orthopedic surgeons. Early diagnosis and strict adherence to the specialized regimen are essential for maximizing skeletal health, reducing the need for corrective orthopedic surgery, and improving long-term quality of life.