Tumor-Induced Osteomalacia

Introduction

Several illnesses can result from tumors since the effects of cancer on the system are invasive. Osteomalacia, known for softening or weakening bones, is one among them. Low levels of phosphate are the ones to induce inadequate bone mineralization in people sustained or being sustained with certain tumors, not every cancer. According to the report, the rare condition has affected about 500 people worldwide. Delayed diagnosis or misdiagnosis is considered the primary reason behind the development of these abnormal symptoms concerning osteomalacia. In addition, it is known to have been elapsed for several years for an individual to receive an accurate diagnosis and appropriate treatment.

What Is Tumor-Induced Osteomalacia?

Tumor-induced osteomalacia, often called oncogenic osteomalacia and oncogenic hypophosphatemic osteomalacia, is a rare syndrome of certain small endocrine tumors characterized by abnormal vitamin D and phosphate metabolism. This is due to the mechanism by which these tumors secrete a substance known as fibroblast growth factor 23 (FGF 23). The factor inhibits the absorption of phosphate, an element responsible for strengthening the bones. Therefore, the condition is in regard to three predominant features, including bone concern and biochemical abnormalities.

• Osteomalacia- Weakening and softening of the bones.

• Hyperphosphaturia- Increased levels of phosphate in the urine.

• Hypophosphatemia- Low concentration of phosphate in the blood.

What Causes Tumor-Induced Osteomalacia?

The tumors are the causative determinant to induce osteomalacia since they contribute to the development of bone weakness after cancer. The oncogenic osteomalacia results when a tumor secretes a factor called fibroblast growth factor 23. This growth factor inhibits the action of the kidney in the absorption of phosphate. So, tumor-induced osteomalacia is described and categorized as a paraneoplastic phenomenon, whereas paraneoplastic is known for the syndrome occurring as a result or consequence of a tumor. The majority of such tumors are benign and slow-growing but with symptomology of rickets and osteomalacia. The commonly associated tumors are the following.

• Benign mesenchymal tumors such as phosphaturic mesenchymal tumors and hemangiopericytoma.

• Malignant forms of mesenchymal tumors have also been reported with oncogenic osteomalacia, including fibrosarcoma and osteosarcoma.

What Is the Pathogenesis of Tumor-Induced Osteomalacia?

The Fibroblast growth factor 23 is the main culprit of tumor-induced osteomalacia. This determinant inhibits phosphate absorption in the kidney and phosphate transport in the renal tubules, decreasing kidney cortisol production. Tumor production of FGF-23, matrix-extracellular phosphoglycoprotein, and secreted frizzled-related protein four are pathogenically involved in hypophosphatemia.

What Are the Risk Factors of Tumor-Induced Osteomalacia?

Tumor-induced osteomalacia is generally characterized by the development of tumors producing the hormone known as fibroblast growth factor, resulting in low phosphate levels in the system. So, the primary risk factor is the presence of these kinds of tumors called phosphaturic mesenchymal tumors (PMT). The other risk factors for tumor-induced osteomalacia include:

• The presence of phosphaturic mesenchymal tumors is a significant risk factor. They can be small and slowly progressive.

• Though tumor-induced osteomalacia can affect people of any age, it is more commonly seen in adults between 30 and 60 years of age.

• In rare events, tumor-induced osteomalacia can be associated with genetic conditions like multiple endocrine neoplasias (MEN) and McCune-Albright syndrome.

• There is no gender predilection for tumor-induced osteomalacia. Both men and women are equally affected.

What Are the Signs and Symptoms of Tumor-Induced Osteomalacia?

Bone and muscle concerns are the predominant features of tumor-induced osteomalacia. The signs and symptoms vary from individual to individual, ranging from mild to severe degrees. The common signs of oncogenic osteomalacia include the following.

• Myalgia or muscle pain.

• Muscle weakness. Reduced strength of muscles seems apparent.

• Bone pain of a throbbing, aching, or probing nature.

• Fatigue.

• Recurrent episodes of fracture due to increased susceptibility. This is due to the abnormal decrement in bone strength.

• Pathologic fractures are secondary to infection, tumors, and inherited bone illnesses.

Subsequently, children with tumor-induced osteomalacia present these symptoms.

• Difficulty in walking.

• Stunted growth.

• Skeletal deformities such as rickets.

How Is Tumor-Induced Osteomalacia Diagnosed?

Medical healthcare professionals elicit an extensive physical examination, analyzing the medical records and tumor history. In addition, the individual is investigated for pain intensity and bone concerns. However, routine laboratory tests do not seem compelling. Instead, biochemical investigations are recommended to trace low phosphate levels, low serum levels of 1,25 dihydroxy vitamin D, and increased alkaline phosphatase concentration. Then the doctors prescribe urine laboratory tests. There prevails increased susceptibility with inappropriately increased urine phosphate levels in terms of hypophosphatemia. The diagnosis is confirmed with the measurement of the factor FGF23.

Following the detection of biochemical abnormalities, healthcare professionals detect the causative tumors with scanning techniques. The gallium 68-DOTA octreotate positron emission tomography technique is the best and most effective way. Other methods include the following:

• Indium- 111 octreotide scan.

• Computed tomography (CT).

• Magnetic resonance imaging (MRI).

How Is Tumor-Induced Osteomalacia Managed?

The treatment is aimed at the intervention of both tumor and osteomalacia. The intervention begins as soon as the causative tumor is detected. The treatment of tumor-induced osteomalacia comprises either one or a combination of drug and surgery therapy.

Medication

Drug treatment is recommended in cases of undetermination of underlying tumors. Calcitriol and phosphate supplementation is generally prescribed. Tumors expressing somatostatin receptors seem responsive and effective against octreotide. The doctors prescribe Cinacalcet administration when identified with the persistence of hypophosphatemia condition even with the calcitriol and phosphate supplements.

Surgical Intervention

Tumor resection is the ideal surgical treatment for oncogenic-induced osteomalacia and other states. This could eventually culminate in the modification and correction of hypophosphatemia in about a few hours of surgical resection.

Rehabilitation

The intervention of skeletal abnormalities takes up to several months. Physical intervention and rehabilitation are followed by medical management as a means to improve muscle tone, posture, and overall quality of life. In addition, the therapists will address the following concerns:

• Pain and discomfort concerning the joint over time.

• Joint stiffness.

• Improvement of joint mobility and, thus, functionality.

• Muscle spasms and muscle tension.

• Optimal motion.

• Muscle strength.

• Improvement in range of motion.

• Enhancement of the function in the specified joint area.

• Therefore, the quality of life overall.

Conclusion

The tumor-induced osteomalacia is a rare condition, though. Delayed series of actions in recognition and diagnosis is an unapparent incitement for this kind of osteomalacia. Therefore, it is vital to be aware of these states since early treatment is the key to the prevention of progression. Education and awareness are to be elevated means for the medical community and people to diagnose and manage this debilitating condition, tumor-induced osteomalacia, effectively.