METABOLIC BONE DISEASES - Rickets, Scurvy, Osteomalacia.

Relevant to ug and pg medical students

1. SCURVY RICKETS OSTEOMALACIA PRESENTED BY- Dr. ARUN CHATURVEDI DNB RESIDENT

2. SCURVY Scurvy is disease caused by severe Vitamin C deficiency which presents with joint effusions, swelling over long bones, bleeding gums, loosening of teeth, hematuria , and susceptibility to hemorrhage . Diagnosis is made based on history, clinical and radiological picture, and resolution of symptoms following vitamin C administration. Lab tests are usually not helpful. Treatment is prompt administration of Vitamin C.

3. RISK FACTORS elderly, especially men who live alone chronic malnutrition overcooking destroys vitamin C alcoholic smokers malabsorptive conditions (Whipple's disease, inflammatory bowel disease, cancer chemotherapy) PATHOPHYSIOLOGY humans are unable to synthesize L-ascorbic acid because the enzyme L- gluconolactone oxidase is nonfunctional Vitamin C deficiency leads to decrease in chondroitin sulfate and collagen synthesis and repair impaired intracellular hydroxylation of collagen peptides net effect is altered bone formatin with the greatest effect occuring in the metaphysis defect in  spongiosa  of the metaphysis at the growth plate  

4. PRESENTATION History infant diet consisting of evaporated or condensed milk "tea and toast" diet in elderly Symptoms malaise and fatigue pain bone pain myalgia, because of reduced carnitine production gum bleeding and loosening of teeth hematuria hematemesis hemorrhage iron deficiency

5. PHYSICAL EXAM petechiae and ecchymosis joint effusions  swelling over long bones  because of subperiosteal hemorrhage   scorbutic rosary  ( costochondral separation) angular step-off deformity in children  differentiated from rachitic rosary, which is rounded and nodular  

6. IMAGING RADIOGRAPHS – wrist , knee, sternal ends of ribs FINDINGS the white line of Frankel  widened  zone of provisional calcification between epiphysis and metaphysis Trummerfeld zone  transvese radiolucent band in the  metaphysis  adjacent to the Frankel line also known as the scurvy line Wimberger ring  ring of increased density surrounding  epiphysis Pelkin spur and fracture  metaphyseal spurs and fractures corner sign of Park  metaphyseal clefts thin cortices ("pencil-point" cortex)  decreased trabeculae with  ground-glass osteopenia   subperiosteal elevation  epiphyseal separation fractures and dislocations

7. TREATMENT Non-operative vitamin C replacement oral vitamin C at 250mg qid x 1 week in adults Indications signs and symptoms of scurvy chronic malnutrition

8. RICKETS Rickets is a metabolic bone disease caused by a defect in mineralization of osteoid matrix caused by inadequate calcium and phosphate that occurs prior to closure of the physis . Patients present with characteristic features such as bowing of long bones, ligamentous laxity, brittle bones and enlargement of costal cartilage. Diagnosis is made based on a thorough evaluation of serum labs, clinical features, and radiographic findings. Treatment involves medical management to resolve the underlying etiology of rickets.

9. Pathophysiology Vitamin D and PTH play an important role in calcium homeostasis  disruption of calcium/phosphate homeostasis poor calcification of cartilage matrix of growing long bones occurs at  zone of provisional calcification leads to increased physeal width and cortical thinning/bowing orthopaedic manifestations include- brittle bones with physeal cupping/widening   bowing of long bones  ligamentous laxity flattening of skull enlargement of costal cartilage (rachitic rosary)  kyphosis (cat back) 

10. PRESENTATION Symptoms listlessness irritability generalized weakness Physical exam    tibial bowing  due to widened proximal tibial physes rachitic rosary enlargement of costochondral junction bowing of knees retarded bone growth muscle hypotonia waddling gait dental abnormalities delayed dental eruption defective enamel pathologic fractures

11. IMAGING RADIOGRAPHS- AP and lateral of affected bone FINDINGS physeal widening  metaphyseal cupping decreased bone density Looser's zones  pseudofracture on the compression side of bone rachitic rosary  prominence of rib heads at the osteochondral junction lower extremity bowing  often  genu varum codfish vertebrae  cat back dorsal kyphosis

12. CLASSIFICATION Vitamin D-resistant (familial hypophosphatemic ) most common form of heritable rickets presents at 1-2 years of age caused by  inability of renal tubules to absorb phosphate    GFR is normal vitamin D3 response is impaired Genetics X-linked dominant   most common form results from mutation in  PHEX gene    leads to increased levels of FGF23, which decreases renal phosphate absorption and suppresses renal 25-(OH)-1α-hydroxylase activity autosomal dominant   results from mutation in  FGF23 leads to decreased FGF23 degradation autosomal recessive results from mutation in  dentin matrix protein 1 (DMP1) gene leads to impaired osteocyte maturation and bone mineralization, and increased levels of FGF23

13. Vitamin D-deficient  (nutritional) results from  decreased dietary intake of Vitamin D rare now that Vitamin D is added to milk presents at 6 months - 3 years of age risk factors premature infants black children > 6 months who are still breastfed  patients with malabsorption syndromes (celiac sprue ) or chronic parenteral nutrition Asian immigrants patients with unusual dietary choices (vegetarian diet) pathophysiology low Vitamin D levels lead to decreased intestinal absorption of calcium low calcium levels leads to a compensatory increase in PTH and bone resorption bone resorption leads to increased alkaline phosphatase levels Vitamin D-dependent  (type I & type II) rare disorder leads to clinical features similar to Vitamin D-deficient rickets but more severe

14. clinical characteristics type I hypotonia , muscle weakness, growth failure, hypocalcemic seizures, joint pain/deformity, fractures in early infancy type II hypotonia , muscle weakness, growth failure, hypocalcemic seizures, growth retardation, bone pain, severe dental caries or dental hypoplasia pathophysiology    type I results from autosomal recessive mutation in  renal 25-(OH)-1 α- hydroxylase    responsible gene 12q14 prevents conversion of inactive form of vitamin D to active form leads to  decreased calcitriol type II results from autosomal recessive mutation in  intracellular receptor for 1,25-(OH)2-vit. D leads to increased calcitriol

15. TREATMENT NON-OPERATIVE calcitriol Indications Vitamin D-resistant (familial hypophosphatemic ) rickets type I Vitamin D-dependent rickets phosphate replacement   Indication - Vitamin D-resistant (familial hypophosphatemic ) rickets Vitamin D Indications Vitamin D-deficient (nutritional) rickets type II Vitamin D-dependent rickets (partial 1,25-(OH)2-vitamin D resistance) Calcium Indication- type II Vitamin D-dependent rickets (total 1,25-(OH)2-vitamin D resistance) Burosumab human monoclonal antibody to FGF-23 approved for the treatment of X-linked hypophosphatemia among children 1 year and olde r.

16. DOSES Calcitriol 20-30  μ g/kg/day split into 2-3 doses in children 0.5-0.75 μ g/day split into 2 doses in adults Phosphate replacement 20-40 mg/kg/day split into 3-5 doses in children 750-1000 mg/day split into 3-4 doses in adults Must be given in combination with active vitamin D (i.e. calcitriol ) in XLH patients, as this prevents the development of secondary hyperparathyroidism as seen in patients treated with phosphate salts alone Vitamin D 5000 IU/day for 6-10 weeks OPERATIVE corrective surgery (multilevel osteotomy) indications severe tibial bowing technique variety of fixation devices including K-wires, plates, intramedullary nails, and/or external fixation

17. OSTEOMALACIA Osteomalacia is a metabolic bone disease where defective mineralization results in a large amount or unmineralized osteoid. Diagnosis is made based on a thorough evaluation of serum labs, clinical features, and radiographic findings. Treatment involves medical management with Vitamin D supplementation and resolving the underlying etiology .

18. Risk factors vitamin-D deficient diets malabsorption e.g. celiac disease renal osteodystrophy hypophosphatemia chronic alcoholism tumors ( tumor -induced osteomalacia )  drugs affecting bone mineralization aluminium etidronate Fluoride drugs associated with vitamin D deficiency phenytoin phenobarbital rifampin cholestyramine cadmium glucocorticoids drugs affecting phosphate homeostasis aluminium-containing phosphate-binding antacid ifosfamide

19. PRESENTATION Symptoms generalized bone and muscle pain fractures of long bones, ribs and vertebrae proximal muscle weakness weakness Fatigue Physical exam waddling gait from hip pain and thigh weakness difficulty rising from chair and climbing stairs

20. IMAGING RADIOGRAPHS FINDINGS Looser's zones ( insufficiency fractures )  medial femoral cortex pubic ramus  scapula fractures (especially in the proximal femur/femoral neck)  biconcave vertebral bodies trefoil pelvis protrusio acetabuli   BONE SCAN increased activity

21. TREATMENT Nonoperative large doses of oral vitamin D (1000IU/day), treat underlying cause specific subgroups of patients on long-term anticonvulsant therapy supplement with 400-800IU/day of vitamin D with hepatobiliary disease supplement with 25(OH)- vit D with renal disease supplement with 1,25(OH)2 vit D

22. SERUM CALCIUM SERUM PHOSPHATE ALKALINE PHOSPHATE PTH 25 (OH) VIT D 1, 25 (OH) VIT D URINARY CALCIUM OSTEOMALACIA LOW LOW HIGH HIGH LOW LOW LOW OSTEOPOROSIS NORMAL NORMAL VARIABLE NORMAL NORMAL NORMAL NORMAL TUMOR INDUCED OSTEOMALACIA LOW VERY LOW LOW LOW LOW LOW LOW OSTEOPETROSIS NORMAL NORMAL HIGH NORMAL NORMAL NORMAL NORMAL

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