Osteomalacia: Symptoms, Types, Causes and Treatment

Osteomalacia is a disorder that softens bones, making them more susceptible to fractures and deformities. Unlike osteoporosis, which involves a loss of bone mass, osteomalacia is characterized by defective bone mineralization. Although it is most often associated with vitamin D deficiency, this condition can result from a variety of underlying causes—including rare tumors and genetic disorders. Understanding osteomalacia is crucial, as its symptoms often go unrecognized, and effective treatment hinges on identifying the exact cause. In this article, we’ll explore the symptoms, types, causes, and treatment options for osteomalacia, drawing on up-to-date clinical research.

Symptoms of Osteomalacia

When osteomalacia develops, the signs can be subtle at first but often become debilitating over time. Early recognition is essential to prevent serious complications, including fractures and skeletal deformities. Many symptoms overlap with other musculoskeletal conditions, making diagnosis a challenge for both patients and clinicians.

Symptom	Description	Commonality	Source(s)
Bone pain	Diffuse, often in hips/lower back/ribs	Very common	2,3,9
Muscle weakness	Especially proximal muscles (thigh/shoulder)	Very common	2,3,9
Fractures	Pseudofractures, especially in ribs/femur	Common	2,3,9
Mobility issues	Difficulty walking, waddling gait	Common	1,3,9

Table 1: Key Symptoms

Understanding Osteomalacia Symptoms

Osteomalacia’s symptoms can be both physically and emotionally taxing. The most frequent complaint is a persistent, dull, and aching bone pain, commonly localized to the hips, lower spine, pelvis, legs, and ribs. Unlike arthritis or localized injury, this pain is often widespread and exacerbated by minor trauma or pressure 2,3,9.

Muscle weakness, particularly in the proximal muscles (those closest to the trunk, like the thighs and shoulders), is another hallmark. This leads to difficulty rising from a chair, climbing stairs, or lifting objects. Over time, the muscle weakness can worsen, severely impacting daily activities and quality of life 2,3.

Fractures are also a significant concern. Osteomalacia often causes characteristic “pseudofractures,” which are incomplete fractures, especially in the ribs, pelvis, and femur. These fractures may occur with minimal or no trauma. In advanced cases, true fractures and skeletal deformities can develop, particularly in weight-bearing bones 2,3,9.

Mobility issues are common, with many patients developing a waddling gait due to pain and muscle weakness. Some may also experience difficulty walking or standing, which can lead to increased risk of falls and further fractures 1,3.

Other symptoms, though less frequently discussed, can include fatigue, tenderness in the bones (especially with pressure), and even emotional distress related to chronic pain and disability. In rare cases of tumor-induced osteomalacia, patients may also report more severe disability and limitations in work or social activities 1.

Types of Osteomalacia

Osteomalacia is not a one-size-fits-all diagnosis; it encompasses several subtypes, each with distinct underlying mechanisms. Understanding these types is essential for accurate diagnosis and targeted treatment.

Type	Main Cause	Distinctive Feature	Source(s)
Nutritional	Vitamin D deficiency	Most common, diet-related	2,3,9
Tumor-induced (TIO)	Excess FGF23 from tumors	Hypophosphatemia, rare	1,4,5,6,7,8
Renal (kidney-related)	Renal tubular dysfunction	Impaired phosphate handling	3,4,7
Hereditary/metabolic	Genetic defects (e.g., XLH)	Early onset, familial	3,11

Table 2: Major Types of Osteomalacia

Nutritional Osteomalacia

By far the most prevalent type, nutritional osteomalacia, is primarily due to vitamin D deficiency. This can stem from insufficient dietary intake, lack of sunlight exposure, or malabsorption syndromes such as celiac disease or complications after bariatric surgery 2,3,9. Aging populations and certain cultural practices that limit sun exposure can also increase risk.

Tumor-Induced Osteomalacia (TIO)

TIO is a rare but fascinating form of osteomalacia caused by tumors—most often benign phosphaturic mesenchymal tumors—that secrete excessive amounts of fibroblast growth factor 23 (FGF23). This hormone disrupts phosphate balance by reducing renal phosphate reabsorption and inhibiting vitamin D activation, leading to low blood phosphate and impaired bone mineralization 1,4,5,6,7,8. TIO can occur at any age and is often challenging to diagnose due to the elusive nature of the underlying tumors.

Renal (Kidney-Related) Osteomalacia

Chronic kidney disease can result in renal osteodystrophy, a condition that includes osteomalacia as one component. Here, the kidneys fail to handle phosphate and vitamin D metabolism appropriately, resulting in low phosphate and vitamin D levels, further impairing bone mineralization 3,4,7.

Hereditary and Metabolic Forms

Some forms of osteomalacia are genetic, such as X-linked hypophosphatemia (XLH), where mutations affect phosphate handling and vitamin D metabolism from early childhood 3,11. These often present with bone pain, weakness, and growth abnormalities in children, but can persist or recur in adults.

Causes of Osteomalacia

Pinpointing the cause of osteomalacia is crucial, as it determines the course of treatment. While vitamin D deficiency is the leading culprit, several other mechanisms can disrupt the bone mineralization process.

Cause	Mechanism	Examples/Notes	Source(s)
Vitamin D deficiency	Reduced calcium/phosphate absorption	Poor diet, low sunlight	2,3,9
Phosphate depletion	Impaired renal handling or excess loss	TIO, renal disease	3,4,5,6,7,8
Genetic disorders	Inherited defects in mineralization	XLH, other rare forms	3,11
Tumors (TIO)	FGF23 overproduction	Phosphaturic tumors	1,4,5,6,7,8
Malabsorption	Poor vitamin D absorption	Celiac, bariatric surgery	9

Table 3: Principal Causes of Osteomalacia

Vitamin D Deficiency

Vitamin D is essential for the absorption of calcium and phosphate from the gut. Deficiency can arise from inadequate sunlight exposure, poor dietary intake, malabsorption syndromes, or certain medications. This deficiency disrupts the supply of minerals necessary for bone hardening, leaving bones soft and prone to bending or breaking 2,3,9.

Phosphate Depletion

Besides vitamin D, phosphate is crucial for bone mineralization. Loss of phosphate—either via the kidneys (as in TIO or familial hypophosphatemic disorders) or from chronic diarrhea—can independently cause osteomalacia. Tumors that secrete FGF23, as seen in TIO, are classic culprits, leading to the kidneys excreting too much phosphate 4,5,6,7,8.

Genetic Disorders

Hereditary forms of osteomalacia, such as X-linked hypophosphatemia, are caused by genetic mutations that impair phosphate reabsorption or vitamin D metabolism. These typically present in childhood but can persist into adulthood 3,11.

Tumors and Paraneoplastic Syndromes

Tumor-induced osteomalacia involves rare, often small mesenchymal tumors that secrete FGF23, disrupting both phosphate handling and vitamin D synthesis. Locating these tumors can be challenging, as they may be anywhere in the body and are frequently very small 4,5,6,7,8.

Malabsorption Syndromes

Conditions that impair absorption in the gut—such as celiac disease, Crohn’s disease, or post-bariatric surgery—can lead to vitamin D deficiency and, subsequently, osteomalacia 9.

Treatment of Osteomalacia

Treatment aims not only to relieve symptoms and heal fractures but to correct the underlying metabolic disturbance. The approach varies depending on the type and cause, making accurate diagnosis essential.

Treatment Approach	Target/Indication	Outcome/Goal	Source(s)
Vitamin D supplementation	Nutritional deficiency	Restore mineralization	2,3,9
Phosphate supplementation	Hypophosphatemic forms	Correct low phosphate	4,5,7,8
Tumor resection	Tumor-induced osteomalacia (TIO)	Potential cure	8,12
Medication (Burosumab)	TIO/XLH (when tumor cannot be removed)	Inhibit FGF23, improve phosphate	10,11
Treat underlying disease	Malabsorption, kidney disorder	Restore normal metabolism	3,9

Table 4: Main Treatment Strategies

Treating Nutritional Osteomalacia

For individuals with vitamin D deficiency, repletion with high-dose vitamin D is the cornerstone of therapy. This may be combined with calcium supplements if dietary intake is insufficient. Most patients respond well, with resolution of pain and muscle weakness and gradual healing of bone lesions 2,3,9.

Managing Tumor-Induced Osteomalacia (TIO)

The definitive treatment for TIO is surgical removal of the causative tumor, which leads to rapid normalization of phosphate levels and symptom resolution in most cases 8,12. However, these tumors are often small and hard to find, requiring advanced imaging techniques such as PET scans or octreotide scintigraphy for localization 4,8.

If the tumor cannot be located or is inoperable, medical management with phosphate supplements and active forms of vitamin D (such as calcitriol) is used to control symptoms, though this approach can be cumbersome and may have side effects 4,5,7.

Newer Therapies: Burosumab and Beyond

Recent advances have brought targeted therapies such as burosumab, a monoclonal antibody against FGF23, into clinical use for both TIO (when tumors can't be removed) and hereditary hypophosphatemic osteomalacia (like XLH) 10,11. Burosumab normalizes phosphate metabolism, improves bone mineralization, and enhances quality of life, with an acceptable safety profile. Other options under investigation include FGFR inhibitors and image-guided tumor ablation 7,10,11.

Addressing Secondary Causes

When osteomalacia results from malabsorption (e.g., celiac disease, bariatric surgery), treating the underlying condition and supplementing vitamin D and calcium are essential. For kidney-related osteomalacia, managing renal disease and correcting biochemical abnormalities are key 3,9.

Monitoring and Follow-up

Regardless of cause, all patients benefit from monitoring of serum calcium, phosphate, vitamin D, and parathyroid hormone levels. Bone density scans and, in some cases, bone biopsies can help assess treatment response. Long-term follow-up is important, particularly in cases of TIO due to the risk of tumor recurrence 8,12.

Conclusion

Osteomalacia is a multifaceted disorder of bone mineralization with diverse causes and presentations. Early recognition and targeted treatment can reverse symptoms and prevent serious complications.

Key points:

• Symptoms: Chronic bone pain, muscle weakness, fractures, and mobility issues are common.
• Types: Includes nutritional, tumor-induced (TIO), renal, and hereditary forms.
• Causes: Most often due to vitamin D deficiency, but can result from phosphate loss, tumors, or genetic disorders.
• Treatment: Depends on the cause—ranging from vitamin D supplementation to surgical tumor removal or targeted therapies like burosumab.

With advances in diagnostic tools and therapies, the outlook for patients with osteomalacia continues to improve. Heightened awareness and a multidisciplinary approach are essential for optimal care.