The human skeleton functions as a dynamic system, adapting flexibly to various physical stresses arising from activities such as work, sports, or movement. This dynamic process leads to constant bone remodeling. However, in rickets and osteomalacia, this process is disrupted, resulting in bone softening and weakening.

Rickets refers to pathological changes in the growth plates of bones, while osteomalacia describes insufficient mineralization of pre-existing bone tissue. All forms of rickets are accompanied by osteomalacia. In adults, whose growth plates have already closed, only osteomalacia occurs.

In the growth plates, chondrocytes - cells responsible for cartilage growth - undergo various developmental stages (chondrogenesis). These cells grow and store calcium and phosphate to enable mineralization. At the end of this process, chondrocytes die off and are replaced by a new structure, the primary spongiosa (osteogenesis). However, this conversion of cartilage (endochondral ossification) requires sufficient phosphate. If phosphate is lacking, chondrocytes cannot die off, disrupting the process and causing the typical symptoms of rickets. Simultaneously, there is reduced mineralization throughout the skeleton, known as osteomalacia.

There are three types of rickets, depending on the cause:

Calcipenic Rickets is the most common form of rickets and results from a deficiency in vitamin D and calcium, often due to poor nutrition or inadequate calcium intake. Vitamin D, produced in the skin through UVB exposure, is essential for calcium absorption in the intestine. When deficient, the body absorbs less calcium, leading to an increase in parathyroid hormone (PTH) levels. This compensatory hormone works to maintain blood calcium levels but results in phosphate loss and a weakened bone structure.

In newborns and infants, symptoms may include seizures or muscle weakness. After six months of age, classic signs of rickets, such as bow legs and joint swelling, often appear. Older patients frequently report nonspecific symptoms like muscle pain and general weakness.

Diagnosis typically involves a detailed medical history and laboratory tests, showing high PTH and alkaline phosphatase (ALP) levels and low 25(OH)D levels. X-ray imaging is crucial for confirming rickets, while a bone biopsy is necessary to diagnose osteomalacia.

The treatment for calcipenic rickets includes supplementation with vitamin D and calcium for at least 12 weeks. It is important to note that phosphate supplementation is contraindicated, as it can worsen the condition. Specific forms, such as renal or hepatobiliary osteodystrophy, require tailored therapies, while genetic disorders necessitate individualized treatments.

Phosphopenic Rickets is a condition caused by increased phosphate excretion through the kidneys. The most common form of this disease is X-linked dominant hypophosphatemia (XLH), which arises from a mutation in the PHEX gene, leading to increased production of the hormone FGF23. As a result, the body retains less phosphate and produces less calcitriol (active vitamin D).

In diagnosing this condition, young children often present with symptoms such as bow legs, short stature, and dental abscesses. On X-ray, the bones may appear unusually dense. Laboratory tests typically show low phosphate levels in the blood, making it important to calculate the TmP/GFR ratio to confirm the diagnosis. Genetic testing is often required as well.

Treatment involves supplementing with phosphate and calcitriol to increase the levels in the body. Alternatively, Burosumab, an antibody that blocks the FGF23 hormone and enhances phosphate absorption, can be used. The dosage of Burosumab is adjusted based on blood phosphate levels to achieve optimal results.

Monitoring of treatment should be carried out in specialized centers, with regular check-ups every 3 to 6 months. For autosomal-dominant hypophosphatemic rickets (ADHR), oral iron supplementation has been shown to improve phosphate reabsorption. In this context, ferritin serves as a reliable marker for monitoring treatment success.

Hypophosphatasia (HPP) is a hereditary condition caused by a mutation in the ALPL gene, which reduces the activity of a crucial enzyme, alkaline phosphatase. This enzyme helps break down substances like inorganic pyrophosphate (PPi). When this enzyme is deficient, PPi accumulates in the body, preventing proper mineralization of bone and cartilage and leading to disorders like rickets and osteomalacia. In severe cases, HPP can also cause seizures associated with vitamin B6 deficiency.

The symptoms of HPP vary widely, depending on the severity of the condition. The most severe forms often appear perinatally or in early childhood, with complications such as respiratory issues, muscle hypotonia, craniosynostosis, and high mortality rates. In children, early loss of primary teeth, bone deformities, and joint pain are common. Adults may experience chronic pain and poorly healing fractures. Due to the variability in symptoms, diagnosis is often delayed.

The diagnosis of HPP typically involves identifying low serum ALP levels, the presence of characteristic symptoms, and molecular genetic testing to confirm the ALPL mutation. Diagnosing carriers can be challenging, as symptoms vary significantly in expression.

Since 2012, enzyme replacement therapy with Asfotase alfa has been available, significantly improving survival and respiratory function in HPP patients. This therapy is administered subcutaneously three times a week and aims to restore the activity of the deficient alkaline phosphatase, thereby enhancing bone and cartilage mineralization.

Treatment is managed in specialized centers, where patients are regularly monitored. Key parameters include growth, motor development, pain levels, and laboratory values such as calcium, phosphate, and vitamin B6 levels. Prognosis improves with older age at the time of diagnosis. Thanks to enzyme replacement therapy, even severely affected patients now have a survival rate exceeding 85%, substantially improving their quality of life and long-term outlook.

In summary, rickets and osteomalacia are serious disorders characterized by impaired skeletal mineralization, with diverse causes and clinical features. Early diagnosis and targeted therapy are crucial to improving the quality of life and preventing long-term complications. While rickets predominantly affects children, osteomalacia is more commonly seen in adults. Advances in research and treatment, such as enzyme replacement therapy for hypophosphatasia, offer new hope and significantly enhance the prognosis for patients with these conditions.

Sources: 

Die Techniker. (2024, Januar 24). Was versteht man unter Rachitis und Osteomalazie? Die Techniker. Source

Tischlinger, K., & Högler, W. (2022). Verminderte Mineralisation des Knochens: Rachitis und Osteomalazie. Monatsschrift Kinderheilkunde, 170(2), 169–182. Source