Last Updated on March 16, 2025
Osteomalacia is a metabolic bone disease where defective mineralization results in bone softening due to a large amount of unmineralized osteoid.
Osteomalacia (mollities ossium) is characterized by softening of the bones because of an accumulation of osteoid tissue. Osteoid is the bone matrix that is mineralized to form bone.
Rickets and osteomalacia are identical in pathology. The only difference is that rickets occur before the closure of physis whereas osteomalacia occurs after closure. Because the bones grow at physes, the longitudinal bone growth is not affected in osteomalacia.
Dietary vitamin D deficiency is the most common cause of osteomalacia worldwide. However, in the United States, gastrointestinal disorders causing vitamin D deficiency and hypophosphatemic osteomalacia are the most common. Gastric bypass surgery for morbid obesity is now emerging as the leading cause of vitamin D deficiency.
Other causes that affect bone mineralization also lead to rickets and osteomalacia.
Normal healthy bone consists of strong meshwork called matrix which is made of protein and minerals like calcium and phosphorus. Bones continuously maintain and repair themselves by removing tiny areas of old bone and replacing them with new bone. Calcium in bone is the main mineral of the bone.
The strength of the bones depends on the amount of minerals in the matrix.
The process of laying down minerals in the bone is called bone mineralization.
From absorption to deposition on the bone, vitamin D plays a major role in calcium and phosphorous metabolism.
Osteomalacia develops when bones don’t get enough of the minerals they need and become soft. This leads to weakening of the bones and problems because of that.
Causes of Osteomalacia
Osteomalacia is usually caused by a prolonged lack of vitamin D or some defect in the mineralization process.
Vitamin D Deficiency
Vitamin D promotes the absorption of calcium absorption by the gut. It is not available in the diet unless it is fortified.
- Nutritional Deficiency: This may happen due to
- Dietary deficiency (fortification)
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- Decreased exposure to sunlight
- Use of sunscreens
- Use of clothing that does not let skin exposed to the sun(often due to cultural reasons)
- Increased or dark skin pigmentation
- Morbid obesity
- Malabsorption syndrome
- Decreased exposure to sunlight
- Pseudovitamin D Deficiency (Vitamin D Dependent Osteomalacia): Genetic disorder that prevents the body from forming calcitriol.
- Drug-Induced Vitamin D- Deficient State: Anticonvulsants (e.g., phenytoin), tranquilizers sedatives, muscle relaxants, and oral antidiabetic agents induce hepatic enzymes that interfere with hydroxylation and conversion of vitamin D.
- Other Causes Leading to Vitamin D Deficiency
- Renal disease affecting vitamin D synthesis.
- Intoxication with diphosphonate, fluoride, aluminum
- Autonomous hyperparathyroidism
- Mesenchymal tumor
Tumor-Induced Osteomalacia
This is also called paraneoplastic syndrome or oncogenic osteomalacia caused by bone or soft tissue tumor. It leads to renal phosphate wasting.
The tumor secretes a humoral factor called phosphatonin that leads to increased phosphate excretion, ultimately causing hypophosphatemia and osteomalacia.
Primary Vitamin D—Resistant Familial Hypophosphatemia
Familial hypophosphatemia is inherited as a sex-linked dominant trait. It is expressed first as rickets and later as osteomalacia in the adult. It is characterized by hypophosphatemia that is present throughout life. However, every patient does not develop the disease. Hypophosphatemia impairs bone formation by interfering with the function of osteoblasts
Phosphate Depletion
The prolonged use of phosphate-binding nonabsorbable antacids causes phosphate depletion and osteomalacia. Marked muscle weakness is typically associated with a very low serum phosphorus level.
Renal Diseases
Renal tubular acidosis leads to low plasma phosphorus levels. Chronic renal disease diminishes the ability of the glomeruli to excrete phosphate resulting in hyperphosphatemia, which in turn causes secondary hyperparathyroidism.
Hypophosphatasia
Hypophosphatasia genetic condition that leads to very low plasma alkaline phosphatase levels.
Pathophysiology of Osteomalacia
The basic pathologic finding is an excess of persisting osteoid seams. There is a normal degree of osteoclastic activity going on. Similarly, osteoblastic activity goes on and layer upon layer of osteoid tissue (matrix) is formed. The development of osteoid is most pronounced at sites of maximal stress and strain. Normally, in due course,e the osteoid is mineralized and bone tissue is formed But in patients with osteomalacia following events happen to create inadequate bone mineralization that leads to the persistence of osteoid that softens the bone where it is present.
Following are stages of this development.
- Preosteomalacia- In its early stages, deficient vitamin D leads to increased serum alkaline phosphatase and parathyroid hormone levels. There is an increased bone turnover. It is also called hypovitaminosis D osteopathy stage I
- In stage II, there is a progressive accumulation of unmineralized matrix (or osteoid) with some preservation of mineralization.
- In stage III, there is a complete stoppage of mineralization occurs
Softening of bones leads to bending of bones at stressful regions and could lead to grotesque deformities.
Presentation of Osteomalacia
Osteomalacia is a very subtle disease with no specific presentation. Osteomalacia symptoms can be so vague and nonspecific that they can easily escape the attention of the physician. Some symptoms are highly specific and often diagnostic.
Earlier presentations are often vague and a high degree of suspicion is necessary to catch osteomalacia in the early stages.
In patients with the genetic forms of osteomalacia and those with childhood celiac disease, residual deformities of rickets with associated short stature may be seen.
Bone pain in osteomalacia may occur and it worsens on weight-bearing, muscle contraction and is rarely relieved completely by rest. Pain is symmetric and involves the lower back, later spreading to the pelvic girdle, hips and upper thighs, and ribs. There is tenderness on the percussion of bones, especially over the tibial shins.
Not all patients have pains though and pain intensity does not correlate with calcium levels.
Some patients may show weakness in the proximal muscles of the limb. There is little muscle wasting and it does not correlate with the severity of weakness.
The patients complain of difficulty in rising from a chair, walking up or downstairs.
Due to the inability to lift the leg off the ground and the pain because of hip and quadriceps weakness, patients walk with a characteristic gait called waddling gait.
Deformities, particularly of weight-bearing bones can be seen in severe cases.
Scoliotic and kyphotic deformities of the spine develop.
The pressure of the femoral heads produces coxa vara [decrease in neck-shaft angle] deformities of the femoral necks and indentation of the acetabulum (protrusion) and the lateral walls of the pelvis [also known as protrusion acetabuli]
On examination, if there is a complaint of bone pains, lateral compression of the ribs or of the pelvic girdle and compression of the sternum can elicit pain in mild to moderate cases. An acute onset of localized pain and tenderness may signify an incomplete fracture. Sometimes these can progress to complete fractures and the patient presents with that.
The patient may also have signs of any underlying disease.
Skeletal deformity can occur in the vertebral bodies and skulls. There may be a forward projection of the breastbone (pigeon chest) and deformities of the spine, including scoliosis or kyphosis.
Dental deformities and a decrease in reflexes may be present.
Differential Diagnosis
- Hyperparathyroidism
- Osteitis fibrosa
- Paget’s disease of bone
- Multiple myeloma
- Chronic excessive fluoride ingestion
- Biphosphonate overdose
- Aluminium toxicity.
Lab Investigations
- Normal blood counts
- A high concentration of serum alkaline phosphatase in most of the patients
- Low calcium level, and low phosphate level in case of Vit D deficiency
- Related Studies
- Liver function test for knowing chronic liver disease
- Renal function tests to know about kidney disorders
- Calcium Studies- Fecal calcium is usually increased in malabsorption
- Phosphorus Studies- Low serum phosphate except in chronic glomerular insufficiency, which causes hyperphosphatemia
- Parathyroid Hormone -Abnormally high value [despite normal calcium]
Imaging
X-rays
X-rays may be normal in mild cases. Advanced cases may show Looser zones are common findings on x-rays. The skeleton is diffusely rarefied, and the cortices are thinned [effect of compensatory hyperparathyroidism]
Looser’s zones are transverse, bilaterally symmetrical lucent bands that extend incompletely across the bones and give the appearance of fractures. They are believed to represent incomplete fractures that have healed by callus consisting of osteoid tissue persisting for lack of calcium.
Sometimes, Looser’s line or zone may be the only evidence of osteomalacia. It occurs repeatedly at characteristic points
- Neck of the femur
- Pubic and ischial rami
- Ribs
- Axillary edge of the scapula immediately below the glenoid.
- Metatarsals
- Medial aspect of the shafts of long bones
Looser’s zones are bilaterally symmetrical and are seen only in patients with osteomalacia and rickets.
There is no subperiosteal resorption of bone in contrast to hyperparathyroidism. The presence of lamina dura (hard bone in the dental socket) can differentiate osteomalacia from hyperparathyroidism where it is absent.
** Looser’s zones invariably heal when the cause of the osteomalacia is identified and appropriate treatment is given.
As a result of bone softening, bending deformities are seen. Vertebral softening may lead to biconcave configuration, resulting in the characteristic ‘’codfish’’ spine. Compression fractures often occur.
Changes in bone shape such as protrusio acetabuli can be seen in severe cases.
CT/MRI
MRI and CT may be required to evaluate pathological fracture and soft tissue damage.
DEXA
DEXA scanning will show decreased bone density.
Bone Scan
A bone scan will show increased skeletal uptake of a radioactive isotope in the ribs and near joints.
Treatment for Osteomalacia
Treatment of osteomalacia requires multiple approaches.
- Correction of the deficiency
- Treatment of the underlying cause
- Deformity Correction
Correction of the Deficiency
Adults with osteomalacia should be given a daily dose of 10,000 IU or a weekly dose of 60,000 IU of vitamin D3 [Cholecalciferol] to restore the depleted reserves.
A maintenance dose of 1,000-2,000 IU calciferol daily or 10,000 IU weekly is adequate after that.
Calcium supplementation should be done along with.
Generally, the oral treatment is preferred. In adults with severe malabsorption or where oral therapy cannot be given, an intramuscular dose of 300,000 IU calciferol monthly for three months followed by the same dose once or twice a year may be considered.
Patients with liver disease should receive 25 dihydroxy vitamin D3 and those with kidney disease should receive 1,25 dihydroxy vitamin D3.
Patient well-being improvement is noted in the first few weeks. Levels of serum alkaline phosphatase and parathyroid hormone would start decreasing within a few months but would normalize in a year or so.
Bony changes would take many months to heal.
Vitamin D is contraindicated in patients with
- Hypercalcaemia
- Metastatic calcification
- Primary hyperparathyroidism
- Renal stones
- Severe hypercalciuria.
In renal tubular disorders and hypophosphatemia, acidosis is corrected by bicarbonate and an adequate phosphate intake of 3-5 g/day. Small doses of 1,25-dihydroxycholecalciferol may also be required.
Treatment of Underlying Cause
Nutritional causes and lifestyle causes should be addressed. Any underlying disease should be treated.
- Diet: A daily dose of 400 IU or 10 micrograms would help to prevent a simple vitamin D deficiency at risk healthy adults. A double dose may be needed in people with very high risk. Foods rich in calcium like dairy products, sardines, tofu, and fortified products should be consumed.
- Sun Exposure: Frequent short spells in summer, without sunscreens, may provide enough vitamin D.
- Supplements: Vitamin D3 supplements should be taken if sun exposure is not sufficient
Deformity Correction
It is not needed often but severe deformities may pose challenges in carrying out requisite activity. These should be addressed on an individual basis
Prognosis
The outcome of treatment of vitamin D deficiency is generally very good. The overall prognosis depends on the underlying disease.
References
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Cianferotti L. Osteomalacia Is Not a Single Disease. Int J Mol Sci. 2022 Nov 28;23(23):14896. [Pubmed Link]
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Francis RM, Selby PL. Osteomalacia. Baillieres Clin Endocrinol Metab. 1997 Apr;11(1):145-63. doi: 10.1016/s0950-351x(97)80569-1.
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Bosman A, Palermo A, Vanderhulst J, De Beur SMJ, Fukumoto S, Minisola S, Xia W, Body JJ, Zillikens MC. Tumor-Induced Osteomalacia: A Systematic Clinical Review of 895 Cases. Calcif Tissue Int. 2022 Oct;111(4):367-379. doi: 10.1007/s00223-022-01005-8. Epub 2022 Jul 20.
