Metabolic Bone Disease Osteolysis (i.e.—hyperparathyroid states) Defective Bone Formation Inadequate mineralization of osteoid (RICKETS) Defective osteoid production (aka Osteoporosis) Nutritional sec. Renal sec. Primary HAC Osteogenesis imperfecta Renal sec. Decr. Ca or P VITAMIN D DEF. Hepatic anticonvulsant

 Regulates calcium and phosphorus levels in the body (calcium homeostasis)  Promotes absorption of calcium and phosphorus from the intestine  Increases bone mineralization  Increases reabsorption of calcium and phosphorus by renal tubules  Maintains healthy bones and teeth

0 nM > 100 nM Rickets Secondary hyperparathyroidism Impaired intestinal calcium absorption Reduced bone volume with normal mineralization Osteopenia

 USUALLY HYPOVITAMINOSIS D --inadequate intake --disorders of vitamin D metabolism --renal failure (decreased synth. Of 1, 25-(OH)2-vitD—the most active)  Decreased Calcium or phosphorus intake (e.g.—inappropriate feeding of renal diets)

Factors Effecting Vit. D Status 1)Geographic location 2)Seasons 3)Skin pigmentation 4)Cultural practices 5)Living conditions/jobs 6)Diet 1)Geographic location 2)Seasons 3)Skin pigmentation 4)Cultural practices 5)Living conditions/jobs 6)Diet

Dietary Renal failure Liver disease Pancreas/small intestinal dz Hypoparathyroidism

METABOLIC CONTROLS of VIT. D ACTIONS METABOLIC CONTROLS of VIT. D ACTIONS 25 (OH) D3 1, 25 (OH) 2 D3 24, 25 (OH) 2 D3 KIDNEY (-)(-)(-)(-) (+) BONE OSTEOCLAST OSTEOCLAST activity MATRIX BREAKDOWN Ca ++ OSTEOBLAST OSTEOBLAST differentiation make more MATRIX (+) (+) PTH (+) (-)(-)(-)(-) (+) (-)(-)(-)(-)

Etiology of Hypophosphatemia Internal redistribution Re-feeding Acute respiratory alkalosis Hungry bone syndrome Decreased intestinal absorption Inadequate intake (< 100 mg/day) Chronic diarrhea, malabsorption Vitamin D deficiency or resistance Aluminum or magnesium ingestion Increased urinary excretion Primary hyperparathyroidism Secondary hyperparathyroidism Proximal tubule dysfunction Hereditary hypophosphatemic rickets Onchogenic osteomalacia

Rickets  Soft bones  Skeletal deformity (bowed legs)  Bone pain  Increased tendency of bone fractures  Dental problems  Muscle weakness  Growth disturbance Osteomalacia Soft bones Bone pain Bone fractures Compressed vertebrae Muscle weakness

Renal osteodystrophy Renal osteodystrophy Osteopenia, subcortical resorption, lucent metaphyseal bands, widening of metaphysis

"rugger jersey spine"

Diagnosis:  Measuring serum levels of: › 25-hydroxycholecalciferol › PTH › Calcium › Phosphate › Alkaline phosphatase

 Ergo- vs chole- calciferol  IM vs po administration  Daily vs intermittent dosing  Dose amount  Co-administration with Calcium Cholecalciferol Po Intermittent 300,000 iu load Separate

 No pharmaceutical funding support for this talk  In last five years received honoraria, travel and subsistence expenses from: › Proctor and Gamble, Servier, Eli Lilly and Novartis Sunshine vitamin

This 73 year old lady was referred from her GP to ENT with deafness. They asked her to see the rheumatologist Why?

 Disease of bone remodeling  Accelerated bone resorption and formation  Disorganised mosaic pattern bone with increased vascularity and fibrosis  Cause unknown › paramyxovirus, canine distemper › Genetics- susceptibility loci  More common in caucasian  M:F ratio 3:210% in over 70’s

 Bone pain  Joint pain  Deformity  Spontaneous fractures

 Fractures  Deafness  Nerve entrapment  Spinal stenosis  Cardiac failure  Osteogenic sarcoma  Hypercalcaemia (only if immobilized)

 Raised serum alk phos  Urinary hydroxyproline, pyridinoline cross-links  Radiology › cortical thickening › osteolytic, osteosclerotic and mixed lesions › osteoporosis circumscripta › bone scan

Normal

Courtesy of Pierre Delmas, MD. V-shaped “blade of grass” lesion characteristic of lytic phase of Paget’s disease

Courtesy of Pierre Delmas, MD. Primarily sclerotic changes, with enlargement and thickening of long bones Secondary osteolytic front

1976 Courtesy of Pierre Delmas, MD Bowing Cortical thickening

Courtesy of Pierre Delmas, MD. Lytic border

Advanced (Sclerotic) Paget’s Disease: “Cotton Wool” Skull Lytic lesion Diffuse sclerotic changes Courtesy of Pierre Delmas, MD.

Courtesy of Nuria Guañabens, MD. Bony enlargement Diffuse sclerotic changes

Courtesy of Nuria Guañabens, MD. Curved deformity of the femur Cortical thickening Accentuation of trabecular pattern

Courtesy of Pierre Delmas, MD. Lytic lesion Cortical thickening

Fissure fracture

Courtesy of Pierre Delmas, MD.

 Bisphosphonates › calcitonin  Indicated if › Complications › Pain › Deformity › AP 2-3X Upper limit › Skull disease