Osteomalacia

Osteomalacia refers to the softness of bones due to incomplete mineralisation of the bone matrix. It occurs in adults and can also be seen in children where it is referred to as rickets.

🦴 Physiology

Ossification is the process by which bones form. There are 2 mains types of ossification:

1. Endochondrial ossification - this is the most common form and the is the process by which long bones form. It begins with the formation of a cartilaginous model of the bone shape by chondrocytes. This model subsequently becomes ossified by osteoblasts.
2. Intramembranous ossification - this is used in the formation of flat bones such as the skull and sternum. It begins with the differentiation of mesenchymal cells into osteoblasts directly without a cartilaginous model.

The process of ossification begins at weeks 6-7 of embryonic development. This process continues throughout childhood and adolescence as some bones only completely ossify at the age of 25 years old.

Ostebolasts are the secreting cells which secrete collagen which is a major component in bone matrix. They also deposit calcium and phosphate into the bone matrix for bone mineralisation. These minerals then bind to the collagen matrix, initiating the formation of hydroxyapatite crystals. This process is known as calcification, and it solidifies the bone, providing it with the hardness and strength required for its structural functions. Osteocytes, mature bone cells derived from osteoblasts, become embedded in the mineralized bone matrix. They play a role in maintaining bone health and responding to mechanical stresses.

The process of bone mineralization is tightly regulated to maintain mineral homeostasis in the body. Various hormones, such as parathyroid hormone (PTH) and calcitonin, as well as vitamin D, play crucial roles in regulating calcium and phosphate levels in the blood and bone.

Therefore, calcium, phosphate and vitamin D homeostasis is vital for bone formation and bone health:

• Vitamin D
1. 7-dehydrocholesterol is a precursor that is converted to cholecalciferol (vitamin D3) through sunlight exposure. We may also get cholecalciferol through dietary intake.
2. Cholecalciferol is converted into 25-hydroxycholecalciferol (calcidiol) through hydroxylation in the liver.
3. The kidneys then convert calcidiol into 1,25-dihydroxycholecalciferol (calcitriol) through additional hydroxylation with the enzyme 1-α hydroxylase.
4. Calcitriol then serves to increase intestinal calcium and phosphate absorption. It also decreases renal excretion of calcium.

• Parathyroid hormone (PTH)
1. PTH promotes 1-α hydroxylase to produce more calcitriol and increase the serum calcium levels.
2. It encourages calcium and phosphate resorption from the bone by osteoclasts.
3. It decreases renal calcium excretion and increases renal phosphate excretion.
• Calcitonin
1. Calcitonin opposes PTH by inhibiting osteoclast activity and increasing renal calcium excretion to decrease serum calcium levels.
2. Calcitonin not only inhibits bone resorption from osteoclasts but also promotes bone formation by stimulating osteoblasts (although this effect is not as significant as compared to the inhibition of osteoclasts).

Pathophysiology

In both rickets and osteomalacia there are issues relating to defective bone mineralisation. This is due to deficiencies in vitamin D, phosphate or calcium.

The difference in rickets is that it happens in children who still have their epiphyseal growth plates and this is where the defective bone mineralisation occurs, leading to growth impairment, malformation and soft bones during the growth phase of the child

Osteomalacia occurs after epiphyseal closrue and as such the bones are not subject to impaired growth and malformation. However, they are at risk of fractures as they are weaker and softer (due to a greater proportion of osteoid/bone matrix being unmineralised

⚠️ Risk factors

• Prolonged breastfeeding - higher risk of vitamin D deficiency
• Unsupplemented cow's milk formula
• Dietary deficiency of calcium - as low calcium stimulates PTH to increase calcium by bone resorption
• Lack of sunlight - leads to vitamin D deficiency.
• Malabsorption disorders - such as coeliac disease or inflammatory bowel disease.
• Chronic kidney disease - leads to CKD-mineral and bone disorder.
• Darker skin - having more melanin reduces your ability to synthesise vitamin D from the sun, resulting in lower 25-hydroxyvitamin D levels
• Increased demand, such as during pregnancy or breastfeeding

😷 Presentation

Patients with vitamin D deficiency, osteomalacia or rickets may be asymptomatic.

😷

Symptoms of osteomalacia

• Fatigue
• Bone pain
• Muscle weakness
• Muscle aches
• Pathological or abnormal fractures 
• In osteomalacia, we see pseudofractures or Looser zones are also seen. These are incomplete fractures that are seen most commonly in the pubic rami

😷

Symptoms of rickets

• Bone pain
• Lethargy
• Swollen wrists
• Bone deformity
• Poor growth
• Dental problems
• Muscle weakness
• Pathological or abnormal fractures

Bone deformities that can occur in rickets include:

• Bowing of the legs - where the legs curve outwards
• Knock knees - where the legs curve inwards
• Rachitic rosary - where the ends of the ribs expand at the costochondral junctions, causing beadlike lumps along the chest (as if it were a rosary).
• Craniotabes - which is a soft skull, with delayed closure of the sutures and frontal bossing
• Delayed teeth - with under-development of the enamel
• Harrison's sulcus - an indentation on the chest wall around the level of the 6th rib.
• Kyphoscoliosis

🔍 Investigations

We need to first assess for vitamin D deficiency:

⭐️ Serum 25-hydroxyvitamin D is the laboratory investigation for vitamin D:

• <25 nmol/L - vitamin D deficiency
• 25 to 50 nmol/L – vitamin D insufficiency

Other laboratory investigations include:

• Calcium - may be low
• Phosphate - may be low
• Alkaline phosphatase - may be high (ALP is important in driving osteoblast activity)
• Parathyroid hormone - may show secondary hyperparathyroidism.

📷

Imaging

• X-rays - may show:
• Osteopenia (more radiolucent bones)
• Bowing of the legs
• Typical changes such as cupping, fraying, and metaphyseal widening.
• DEXA scan - shows low bone mineral density

🧰 Management

Both rickets and osteomalacia can be cured if adequate supplementation of the missing mineral/vitamin is provided.

X-linked hypophosphataemia (XLH) is an inherited disorder characterised by low levels of phosphate in the blood. Phosphate levels are low because phosphate is abnormally processed in the kidneys, which causes a loss of phosphate in the urine (phosphate wasting) and leads to rickets.

🧰 It may be managed with oral phosphate and vitamin D3 supplements.