Osteomalacia is a metabolic bone disease where defective mineralization results in bone soften 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 which is mineralized to form bone. Like rickets, osteomalacia also affects mineralization of the osteoid.
Rickets and osteomalacia are identical in pathology. The only difference is that rickets occur before closure of physis whereas osteomalacia occur 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. But 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 osteomalacia in US.
Other causes that affect bone mineralization also lead to rickets and osteomalacia.
Normal healthy bone consists 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 are and replacing them with new bone. Calcium in bone is 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 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.
Osteomalacia is different from osteoporosis. Osteoporosis leads to quantum decrease in bone mineral volume without mineralization defect, whereas osteomalacia is associated with a decrease in bone volume and excess osteoid accumulation. Extent of bone mineralization is either near normal or slightly reduced in osteoporosis, whereas it is always absent in osteomalacia.
Causes of Osteomalacia
Osteomalacia is usually caused by a prolonged lack of vitamin D or some defect in mineralization process.
Vitamin D Deficiency
Vitamin D promotes absorption of calcium absorption by the gut and mobilization of mineral from the bone. Probable effects on bone are bone formation and mineralization; effects on the renal tubule are inhibition of calcium resorption and encouraging phosphate resorption.
Our diet supplies us with ergosterol, known as calciferol or Vit D2. Various conditions may interfere with its absorption. Vitamin D3 is also formed from ultraviolet light acting on the precursor substance in the skin. This is converted into 1,25-dihydro vitamin D3 by hydroxylation in liver  and kidney 
Primary deficiency of vitamin D is not seen frequently because vitamin D2 is used to fortify foods. Occasionally it is seen in strict vegetarians who lack exposure to the sun’s rays. Other causes are
- Decreased exposure to sunlight
- Use of sunscreens
- Use of clothing [cultural] which covers skin and enough skin is not exposed to sun
- Increased or dark skin pigmentation
- Inadequate dietary intake
- Morbid obesity
A malabsorption syndrome refers to the clinical picture produced by a wide variety of conditions that reduce the absorptive ability of the small intestine. The main defect appears to be failure to absorb fat and fat-soluble vitamin D, glucose, vitamin A, vitamin B12, and the intrinsic factor.
The dietary calcium combines with fatty acids to form insoluble soaps, which, with the excess of fats and carbohydrates, are excreted in bulky, frothy, foul-smelling stools.
Coeliac disease, biliary obstruction, pancreatitis , and surgical conditions (gastrectomy, gastrojejunocolic fistula) may lead to malabsorption syndromes that effect rapid propulsion of intestinal contents.
Pseudovitamin D Deficiency (Vitamin D—Dependent Osteomalacia)
It is inherited as a recessive trait, and it is probably caused by an inborn error of vitamin D metabolism. It is treated by large doses of vitamin D. This is the most severe and deforming type of rickets and osteomalacia.
Drug-Induced Vitamin D- Deficient State
Anticonvulsants (e.g., phenyltoin), tranquilizers sedatives, muscle relaxants, and oral antidiabetic agents are capable of inducing hepatic microsomal oxidase degradative enzymes that interfere with hydroxylation and conversion of vitamin D to more active metabolites.10-12,14,20 The result is an inadequate amount of circulating 25-OH calciferol, leading to rickets in children and osteomalacia in adults.
Other Causes Leading to Vitamin D Deficiency
- Renal disease causing defective vitamin D synthesis.
- Intoxication with diphosphonate, fluoride, aluminum (antacid ingestion)
- Autonomous hyperparathyroidism
- Mesenchymal tumour
Tumor Induced Osteomalacia (Oncogenic Osteomalacia)
This is also called paraneoplastic syndrome and leads to renal phosphate wasting. It is caused by bone or soft tissue tumor. It could be present from childhood to adulthood.
The tumor secretes a humoral factor called phosphatonin that affects the proximal renal tubules to reduces calcitriol production in the kidney and inhibits phosphate transport which leads to increased phosphate excretion.
Increased phophates excretion causes hypophosphatemia and osteomalacia.
This kind of tumors are called phosphaturic mesenchymal tumors and include both benign and malignant tumors. Commonenst tumor is hemangiopericytoma. Other tumors are osteoblastoma-like tumors, ossifying fibrous tumors, nonossifying fibrous tumors, osteosarcoma and fibrosarcoma.
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, osteomalacia and rickets, retarded longitudinal growth, osteosclerosis, and ligamentous calcification. Hypophosphatemia is present throughout life, but not all patients develop bone disease.
Hypophosphatemia impairs bone formation by interfering with the function of osteoblasts
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 Tubular Acidosis
Because of impaired tubular transport, the kidney is unable to excrete an excess of hydrogen ion and to acidify the urine. The condition is hereditary or acquired and occasionally is complicated by vitamin D—resistant rickets or osteomalacia. The primary biochemical disturbance is a low plasma phosphorus level with a low renal phosphate threshold. The serum calcium level is normal.
When impaired tubular transport is severe and involves many substances such as glucose, phosphate, and amino acids, the condition is termed the Fanconi syndrome. Bone mineral buffers hydrogen ions. The increased demand for neutralizing bases uses up the available calcium, which leaves an inadequate supply for mineralization of osteoid.
Hypophosphatemia and vitamin D resistance are usually associated with chronic systemic acidosis.
Chronic renal diminishes the ability of the glomeruli to excrete phosphate results in hyperphosphatemia, which in turn causes secondary hyperparathyroidism. Acidosis and an elevated blood urea nitrogen level reflect chronic renal failure.
Hypophosphatasia presents clinically as rickets or osteomalacia. It is transmitted as an autosomal recessive and occasionally dominant trait and is characterized by very low plasma alkaline phosphatase and urinary phosphoryl-ethanolamine and pyrophosphate levels.
Pathophysiology of Osteomalacia
The basic pathologic finding is an excess of persisting osteoid seams.There a normal degree of osteoclastic activity going on. Simialrly osteoblastic activity goes on and layer upon layer of osteoid tissue is formed. The development of osteoid is most pronounced at sites of maximal stress and strain. The marrow appears to be vascular and fibrous, especially in patients with secondary hyperparathyroidism.
Following are stages of this development.
In its early stages, deficient vitamin D leads to increased serum alkaline phosphatase and parathyroid hormone levels. There is an increased bone turnover without mineralization defect, and irreversible cortical bone loss.
It is also called hypovitaminosis D osteopathy stage I or preosteomalacia.
In the next stage, hypovitaminosis D osteopathy stage II, there is progressive accumulation of unmineralized matrix (or osteoid) with some preservation of mineralization.
In the last stage, hypovitaminosis D osteopathy stage III, there is complete stoppage of mineralization with no tetracycline uptake, conforming to the traditional descriptions of osteomalacia.
Fractures when occur are usually multiple and heal with an abundant callus formation, but that callus consist chiefly of osteoid, so that union is markedly delayed.
Softening of bones lead 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 high degree of suspicion is necessary to catch osteomalacia in the early stages.
It is quite often missed and patients falsely labeled as fibromyalgia, severe myopathy, unusual pain syndrome,or neurologic disorders of unknown cause. 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
Pain in osteomalacia is felt in bones. It is dull, persistent pain and poorly localized. It is thought to be caused by hydration of the unmineralized bone matrix underneath the periosteum that stretches causing throbbing pain.
The pain worsens on weight-bearing, muscle contraction and often is not relieved by contraction of the muscles during locomotion, 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 percussion of bones, especially over the tibial shins.
Lateral compression of the ribs or of the pelvic girdle and compression of the sternum are useful clinical maneuvers to elicit pain in mild to moderate cases.
Not all patients have pains though and pain intensity does not correlate with calcium levels.
Weakness of proximal muscles of limb is characteristic of osteomalacia. The severity can vary from a subtle to severe disability.
There is little muscle wasting and it does not correlate with severity of weakness.
The patients complaint of difficulty in rising from a chair, walking up or down stairs.
Due to inability to lift the leg off the ground and the pain because of hip and quadriceps weakness, patients walk with 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.
Pressure of the femoral heads produces coxa vara [decrease in neck shaft angle] deformities of the femoral necks and indentation of the acetabulae (protrusion) and the lateral walls of the pelvis [also known as protrusion acetabuli]
An acute onset of localized pain and tenderness may signify an incomplete fracture. These fractures have typical locations and presentation on xray.
Sometimes these can progress to complete fractures.
Patient may also have signs of any underlying disease.
Dental deformities and decrease in reflexes may be present.
- Osteitis fibrosa
- Paget’s disease of bone
- Multiple myeloma
- Chronic excessive fluoride ingestion
- Biphosphonate overdose
- Aluminium toxicity.
Blood counts are often normal. Anemia may be seen in malabsorption syndrome.
More than 80% of adults with osteomalacia have a high concentration of serum alkaline phosphatase.
In typical primary nutritional vitamin D deficiency, the serum calcium level is low or low normal, the phosphorus level is low or normal (most commonly a low normal calcium with a low phosphorus), and the alkaline phosphatase level is moderately elevated.
Increased serum alkaline phosphatase level is the most frequent and the earliest biochemical manifestation. As the vitamin D depletion advances, parathyroid and biochemical markers of bone turnover are increased.
Before performing metabolic studies, attempt should be made to understand if the vitamin D deficiency is the result of inadequate dietary intake, insufficient sunlight, or gastrointestinal disorders that cause malabsorption.
The following studies should be done –
- 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
- Serum calcium is slightly on lower side of threshold or normal [compensatory hyperparathyroidism]
- Decrease in urinary calcium
- Phosphorus Studies
- Low serum phosphate(exception is chronic glomerular insufficiency, which causes hyperphosphatemia)
- Alkaline Phosphatase -Substantially rasied due to osteoblast activity
- Parathyroid Hormone -Abnormally high value [in spite of normal calcium]
- Bone Biopsy –Needed rarely. Excess of excess of unmineralized bone matrix (i.e., osteoid) indicates osteomalacia.
Demineralization and persistent transverse Looser zones are common findings on x-ray. The skeleton is diffusely rarefied, and the cortices are thinned [effect of compensatory hyperparathyroidism]
Looser lines, or pseudofractures, are frequently found.
These are transverse, bilaterally symmetrical lucent bands that extend incompletely across the bones and give appearance like fractures [see x-rays].
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
- Axillary edge of the scapula immediately below the glenoid.
- Medial aspect of the shafts of long bones
Looser’s zones are bilaterally symmetrical and are seen only in patients with osteomalacia and rickets.
These 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. In the spine, the vertebral changes are those that are common to demineralized vertebrae of any cause. The nucleus pulposus expands the disks and indents the endplates of the vertebral bodies, which develop a 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.
Occasionally pseudofractures can occur without osteomalacia.
Imaging is may not required in all cases.
MRI and CT may be required to evaluate of pathological fracture and soft tissue damage.
DEXA scanning will show decreased bone density.
Bone scan will show increased skeletal uptake of radioactive isotope in the ribs and near joints.
It is hardly done today. Iliac bone biopsy will show a failure of mineralisation and wide osteoid seams.
Diagnosis of Osteomalacia
Diagnosis of osteomalacia is generally made on a careful history and physical examination .
A reduced serum calcium × phosphate product and high alkaline phosphatase level in the presence of low 25-hydroxyvitamin D and high PTH makes the diagnosis of osteomalacia highly likely.
Biopsy may be required in selected cases.
Treatment for Osteomalacia
Treatment of osteomalacia requires multiple approaches.
- Correction of the deficiency
- Treatment of the underlying cause
- Education and prevention
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 stores .
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 first few weeks. Levels of serum alkaline phosphatase and parathyroid hormone would start decreasing within few months but would normalize in a year or so.
Bony changes would take many months to heal.
treatment in adults, but may take a year to fall into the reference range.
In kidney diseases, 1,25-dihydroxycholecalciferol should be used with response monitored until alkaline phosphatase level returns to normal.
In renal tubular disorders and hypophosphataemia, the 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.
Any deformity or fracture or other complication should be addressed as well.
Education and Prevention
Education and prevention is providing information about appropriate sunlight exposure, the use of vitamin D supplements, proper diet.
A daily dose of 400 IU or 10 microgrms would help to prevent a simple vitamin D deficiency at risk healthy adults. Double dose may be needed in people with very high risk.
Good sources of calcium include:
- Dairy products like milk, yoghurt and cheese
- Fortified products
- Soya beans and tofu
- Leafy green vegetables like broccoli and cabbage
- Fish such as sardines and pilchards
Diet alone is not sufficient to provide daily vitamin D requirement. Few diets like oily fish, eggs, Vit D fortified products provide vitamin D.
Frequent short spells in summers, without sunscreens, may provide you with enough vitamin D.
Vitamin D3 supplements should be taken by persons where it is not possible to have proper sun exposure.
Serum calcium concentrations should be checked regularly for a few weeks after starting treatment for vitamin D deficiency.
Following that, vitamin D parathyroid hormone calcium concentrations should be checked after 3-4 months of treatment to assess efficacy followed by half yearly check up.
Outcome of treatment of vitamin D deficiency is generally very good. Overall prognosis depends on the underlying disease.
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