Rickets & osteomalacia

slides highlighting the causes, clinical presentation, radiological evidence and treatment of Rickets & osteomalacia.

1. Presented by: Dr. Nikhil Agarwal Rickets & Osteomalacia …

2. Largely collagenous matrix, impregnated with mineral salts and populated by cells. The matrix – Type I collagen fibres (80%) Non-collagenous proteins – mainly sialoproteins ( osteopontin ), osteonectin , osteocalcin ( bone Glaprotein ) and alkaline phosphatases Bone mineral – calcium and phosphate Bone cells : osteoblasts, osteocytes and osteoclasts. Bone composition…

3. Definition … Rickets and osteomalacia are syndromes of diverse etiology, characterised pathophysiologically by a failure of normal mineralisation of bone and epiphyseal cartilage and clinically by skeletal deformity . Osteomalacia by definition means that osteoblasts have laid down a collagen matrix, but there is a defect in its ability to be mineralized .

4. In children, a defect in the mineralization of the osteoid in the long bones and the failure or delay in the mineralization of endochrondal new bone formation at the growth plate leads to the classic skeletal deformities of rickets. However, in adults, the mineralization defect takes on a different character due to the failure of mineralization of newly formed osteoid at sites of bone turnover of periosteal or endosteal apposition.

5. Nutritional rickets or vitamin D–deficiency rickets Vitamin D–dependent rickets Type I or pseudovitamin D–deficiency rickets Type II or hereditary 1-α, 25-dihydroxyvitamin D–resistant rickets Vitamin D–resistant rickets Familial hypophosphatemic rickets or X-linked hypophosphatemic rickets Hereditary hypophosphatemic rickets with hypercalciuria Miscellaneous Renal rickets or renal osteodystrophy Rickets of prematurity Tumor-induced or oncogenic rickets

6. Causes… Phosphopenic – due to inadequate dietary phophate intake or excessive renal tubular loss Primary X-linked dominant Autosomal dominant Autosomal recessive X-linked recessive Hereditary hypophosphatemia with hypercalciuria Secondary Oncogenic osteomalacia Fibrous dysplasia : McCune–Albright syndrome Ifosfamide nephrotoxicity Fanconi syndrome Low dietary phosphate intake Calcipenic – due to calcium deficiency or interruption in the supply, metabolism or utilization of vitamin D Calcium deficiency Nutritional vitamin D deficiency Malabsorption Liver disease Renal insufficiency 25-hydroxylase deficiency Vitamin D dependent rickets type I Vitamin D dependent rickets type I

7. Rickets…

8. Craniotabes

9. Rachitic Rosary

10. Harrison’s Sulcus

11. Genu Varum Windswept Deformity

12. The initial laboratory tests in a child with rickets should include serum calcium, phosphorus alkaline phosphatase parathyroid hormone (PTH) 25-hydroxyvitamin D 1,25-dihydroxyvitamin D 3 urea/ creatinine ; and electrolytes. Urinalysis for glycosuria and aminoaciduria seen with Fanconi syndrome. Investigations…

13. Evaluation of urinary excretion of calcium (24 hr collection for calcium or calcium- creatinine ratio) is helpful if hereditary hypophosphatemic rickets with hypercalciuria or Fanconi syndrome is suspected. Measurement fat-soluble vitamins (A, E, and K), prothrombin time (for vitamin K deficiency) is appropriate if malabsorption is a consideration. Xray wrist and Knee

14. There is thickening and widening of the growth plate , fraying, cupping and splaying of the metaphysis and, sometimes, bowing of the diaphysis .

15. If the serum calcium remains persistently low, there may be signs of secondary hyperparathyroidism: subperiosteal erosions are at the sites of maximal remodelling such as the radial aspects of the proximal and middle phalanges of the middle and index fingers, medial borders of the proximal humerus , femoral neck, distal femur and proximal tibia.

16. Vitamin D is administered orally either as a single dose of 600,000IU or over 10 days (60,000IU daily for 10 days), followed by a maintenance dose of 400-800IU/day and oral calcium supplements (30-75mg/kg/day) for 2 months. If radiologic healing cannot be demonstrated, despite 1-2 large doses of Vitamin D, patient should be evaluated for refractory rickets. TREATMENT OF RICKETS

17. No Healing with two Mega Doses of Vit D (Refractory Rickets) Serum Phosphate Low or Normal Blood pH Low Normal Renal Tubular acidosis High CKD Serum PTH & Calcium PTH: high Ca : low VDDR PTH: normal Ca: normal Hypophosphatemic Rickets

18. X-LINKED HYPOPHOSPHATEMIC RICKETS Most commonly inherited form of refractory rickets. X-linked dominant PHEX gene defective (Phosphate-regulating gene with homology to Endopeptidases on the X chromosome) Impaired proximal tubular reabsorption of phosphates  hypophosphatemia with low 1,25(OH) 2 D3  implying deranged response of renal 1 α hydroxylase to low PO4 Coxa vara , genu valgum / varum , short stature, craniosynostosis , dental abscesses. Treatment: Oral phosphorus (30-50mg/kg in 5-6 equal parts) and 1,25-D ( α - calcitriol )(25-50ng/kg/day).

19. VDDR Type I Mutations in the gene encoding renal 1α-hydroxylase, prevents conversion of 25-D into 1,25-D. Autosomal recessive Low levels of 1,25-D Hypotonia , growth failure, motor retardation, convulsions, anemia. Thickening of wrists and ankles, frontal bossing, widely open anterior fonatanelle , rickety rosary, bony deformities, delayed dentition. Positive Trousseau and Chvostek signs. Treatment with 1,25-D ( calcitriol )(0.25–2 μg /day); concomitantly with calcium with or without phosphate supplements.

20. VDDR Type II Mutations in the gene encoding the vitamin D receptor, end organ resistance to 1,25(OH) 2 D3  virtual abolition of its action, despite its markedly raised levels in circulation. Early onset of rickets, alopecia and ectodermal defects ( milia , oligodontia and epidermal cysts), hypocalcemia , secondary hypoPTH Treatment 3–6 month trial of extremely high-dose vitamin D & oral calcium. (the initial dose of 1,25-D should be 2 μmg /day, but some patients require doses as high as 50–60 μmg /day. Calcium doses range from 1,000–3,000 mg/day) Patients who do not respond to high-dose vitamin D may be treated with long-term intravenous calcium. Prognosis: Poor Alopecia in 50 to 70% cases

21. Operative Procedures… Very young children with deformity, treatment of the metabolic defect supplemented by corrective splinting or bracing. Prepubertal children or adolescents, medical management and bracing usually do not correct an established deformity and early osteotomy is often indicated. The deformities that require surgical correction most often are genu varum and genu valgum .

22. Corrective osteotomy

23. Osteomalacia … Clinical features: Do not present with any overt skeletal signs . Complain of throbbing, aching bone discomfort often worse while sitting or lying in bed. They also have proximal muscle weakness and aching in their muscles, and mild bowing of limbs. Hypotonia . Some weight loss. To make the diagnosis, pressing with thumb or forefinger with some force on the sternum, radius , ulna, or anterior tibia will often result in wincing bone discomfort.

24. Looser’s Zone ( Milkman’s Pseudofractures ) Pathognomonic Looser zones are radiolucent lines that are often penetrating through the cortex perpendicular to the shaft and are most often seen in the medial cortices of the femurs and in the pelvis and ribs, neck of scapula. Caused by rapid resorption and slow mineralisation and may be surrounded by a collar of callus.

25. Trefoil Pelvis

26. Biconcave vertebrae Compression fractures

27. Treatment Of Osteomalacia Vit D 50000 IU / wk X 3-12 weeks Followed by maintenance 800IU /day Along with elemental Calcium 1.5 to 2 g / day

28. Scurvy  (also known as  Barlow disease  in infants) Patients may present with lethargy and malaise, bone pain, bleeding diathesis (e.g. bleeding gums), and impaired wound healing.   Vitamin C is essential for collagen synthesis, acting as a coenzyme to producing cross-linking of collagen fibres . Defective collagen cross-linking compromises skin, joint, bone, and vascular integrity. Radiographic features generalised osteopaenia cortical thinning: “pencil-point” cortex periosteal reaction  due to subperiosteal haemorrhage scorbutic rosary: expansion of the costochondral junctions may relate to the fracturing of the zone of provisional calcification during normal respiration similar to the  rachitic rosary  appearance as seen in  rickets haemarthrosis Wimberger ring sign : circular, opaque radiologic shadow surrounding epiphyseal centres of ossification, which may result from bleeding Frankel line: dense zone of provisional calcification Trümmerfeld zone: lucent metaphyseal band underlying Frankel line Pelken spur: metaphyseal spurs which result in cupping of the metaphysis

29. Osteomalacia Osteoporosis Abnormality in the building process of bone, making them soft Degeneration of already constructed bone, making them brittle Increase in demineralised bone Overall decrease in bone mass Unwell Well Generalised chronic ache Pain after fracture Looser’s zone Absent Phosphate decrease Normal ALP increase normal

30. References… Apley and Solomon System Of Orthopaedics and Trauma 10 th Edition Campbells Operative Orthopaedics 12 th Edition Maheshwari and Mhaskar Essential Orthopaedics Ghai Essential Paediatrics

31. Thank you…

32. Type Causes Inheritance pattern Clinical features Treatment* Nutritional rickets or vitamin D–deficiency rickets Vitamin D deficiency, phosphorus or calcium deficiency (rare), inadequate sunlight exposure, secondary to malabsorption syndromes (IBD, celiac disease, cystic fibrosis [rarely]) NA Skeletal findings, abnormal gait, hypocalcemic tetany /seizures, developmental delay, failure to thrive Replace the deficient nutrient orally; may need to administer vitamin D intramuscularly if rickets secondary to malabsorption . Vitamin D–dependent rickets Type I or pseudovitamin D–deficiency rickets Deficiency of renal 25(OH) D 3 –1-α-hydroxylase Autosomal recessive Younger than two years, hypocalcemic tetany, severe bony changes, seizures Calcitriol ( Rocaltrol ) Type II or hereditary 1-α, 25-dihydroxyvitamin D–resistant rickets Defective interaction between calcitriol and receptor Autosomal recessive Younger than one year, severe bony changes, alopecia Massive doses of calcitriol and calcium Vitamin D–resistant rickets Familial hypophosphatemic rickets or X-linked hypophosphatemic rickets Impaired proximal renal tubular reabsorption of phosphorus and inappropriately normal calcitriol levels X-linked dominant Short stature, leg bowing, dental abnormalities Oral phosphate and calcitriol Hereditary hypophosphatemic rickets with hypercalciuria Impaired proximal renal tubular reabsorption of phosphorus and increased calcitriol Autosomal recessive, autosomal dominant Bone pain, muscular weakness Oral phosphate Miscellaneous Renal rickets or renal osteodystrophy Loss of functional renal parenchyma caused by chronic renal failure leads to mineral derangements and decreased calcitriol production NA Bone pain, arthralgias , fractures, muscle weakness, failure to thrive Vitamin D and phosphate- binding compound Rickets of prematurity Multifactorial NA Osteopenia, fractures Replace dietary deficiencies and minimize iatrogenic causes. Tumor-induced or oncogenic rickets Tumor-induced inhibition of renal 25(OH)D 3 –1-α-hydroxylase NA Fractures, bone pain, muscle weakness Treat underlying malignancy.