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3/2/2017 Metabolic Bone Disease Metabolic Bone Disease Disorders of bone strength, usually caused by abnormalities of mineral (such as calcium or phosphorus), vitamin d, bone mass or bone structure. Lori Bretschneider MSN ,APRN, ONC Metabolic Bone Disease • Recognize Orthopaedic complaints that may be secondary to underlying metabolic bone disease Overview of Bone • Cortical bone: gives strength (80%) • Cancellous (trabecular): metabolic active bone (20%) • Rickets\Osteomalcia • Paget’s Disease • Renal osteodystrophy • Osteoporosis Bone Content • Protein : collagen defects • Mineral: Calcium/Phosphorus • Cells: metabolically active (osteoblasts and osteoclasts) Bone Cells • Osteoblasts: build bone, secrete collagen(osteoid), have estrogen receptors • Osteoclasts: breaks down bone and responsible to reabsorbing • Osteocytes: mature bone cells that is formed when osteoblast becomes embedded in its matrix it has secreted 1 3/2/2017 Bone Cells Bone remodeling Bone Strength Hormone Regulation •Parathyroid Hormone • 60% of bone mass is inherited •Estrogen • 20-40% you can impact • Body only makes as much bone as you need PTH • Main function is to maintain serum calcium • Acts via Vitamin D on kidney and gut to indirectly increase serum calcium • Acts directly on both bone and kidney to increase serum calcium •Testosterone Estrogen • Major effect on bone is to inhibit bone reabsorption • Increase osteoblast activity • Increase bone matrix • Function decrease with age 2 3/2/2017 Testosterone • Androgen hormone that has significant correlation with osteoporosis • Easily will correct osteopenia/osteoporosis with treatment Minerals and Vitamins • Calcium (98% is found in bone) • Phosphorus (85% found in bone) • Magnesium (50-60% found in bones) • Vitamin D Low Calcium Calcium • Forms and maintains bone and teeth • Assists in transmission of nerve impulses • Assists in muscle contraction • PTH is released when calcium is low • PTH stimulates activation of Vit D • PTH and Vit D • Kidneys to retain more calcium • Osteoclasts to break down more bone and release calcium • Stimulate calcium absorption from intestines High Calcium Phosphorus • Thyroid gland releases calcitonin • Critical to bone mineralization • Calcitonin functions to • Filter waste in kidneys • Prevent calcium absorption from kidneys • Limit calcium absorption from intestines • Inhibit osteoclast from breaking down bone 3 3/2/2017 Magnesium • Important to mineralization of bone • Cofactor in over 300 enzyme systems Vitamin D • Fat soluble vitamin • Required for calcium and phosphorus absorption • Regulates blood calcium • Stimulates osteoclasts • Necessary for bone calcification Conversion of Vitamin D Rickets Types 1. Nutritional 2. Hereditary Rickets History • 1650 ,Frances Glisson Cambridge, England first to describe clinical features of rickets • Vitamin D not discovered until 1930’s • Rampant at the turn of the 20th century • Thought to be because of lack of fresh air, sunshine, and exercise, along with poor hygiene • Eradicated for the most part in the 1930’s with cod liver oil and Vitamin D fortified milk Rickets Risk Factors • Inadequate exposure to sunlight • Northern latitudes • Malabsorption problems • Exclusively breast fed infants • Mothers who are Vit D deficient during pregnancy 4 3/2/2017 Rickets Rickets • How much Sunshine Malabsorption Disorders • Spring and summer with 25% exposure (hands, face, neck and arms) 8- 10minute between 10am-3pm • African Americans may need 6x uv exposure • Above the 35 degree latitude little to no Vitamin D can be produced from November to February • Winter with 10% exposure 2 hours at noon • Any resection of small bowel • Celiac Sprue, Short bowel syndrome, cystic fibrosis Rickets Rickets Breast Fed Babies Medications • Breast milk has minimal Vitamin D • Dilantin, Phenobarbital and Rifampin • Supplementation should start around 2 months • Can induce P450 enzyme to accelerate the catabolism of Vitamin D Rickets Rickets • Other Considerations • Darker skin (Black, Hispanic and Asians) interferes with the cutaneous synthesis of Vitamin D Clinical History • Prenatal history • Sunscreen • Dietary history • Babies adopted from overseas • Medical history 5 3/2/2017 Rickets Rickets Sign and Symptoms • Fussy baby • Soft skulls • Bowed legs • Wrist and ankles wider • “Knobby” deformity of wrists, ankles, chest • Fractures Rickets Rickets Rickets Rickets Diagnosis Other lab Calcium: will be low • Lab work: Vitamin D 25OH Phosphorous: will be low • <21-29ng/ml : Vit D insufficiency • <20ng/ml : Vit D deficiency Alkaline Phosphatase: will be high 6 3/2/2017 Rickets Treatment of infants up to a year • 2000IU/day of Vit D3 x 6 weeks or • 50,000 IU Vit D3 once weekly for 6 weeks • One time dose of 600,000 IU IM • Once serum level exceeds 30ng/ml, provide maintenance of 400-1000 IU /day Rickets Dietary Sources of Vitamin D • Cod liver oil 1 tablespoon: 1360 IU • Swordfish 3oz: 566 IU • Salmon 3oz: 447 IU • Tuna, canned in water: 154 IU • Orange juice fortified 1 cup: 137 IU • Milk 1 cup: 124 IU • Yogurt 6oz: 80 IU • Egg, yolk only: 41 IU Osteomalcia Rickets Left Untreated: • Failure to grow • Abnormal spinal curvatures • Skeletal deformities • Dental defects • seizures • Softening of the bones in adults • Characterized by accumulation of increased amount of uncalcified osteoid • Normal delay from osteoid synthesis and mineralization is 3-5 days • In Osteomalcia it may take 3 months or longer Diagnosis Symptoms • No Sign or symptoms in early stages of disease • Vague bone pain and weakness (low back, pelvis, hips, legs and ribs) • Trouble getting up from seated position • Night time pain • Pain with WB • Waddling gait • Labs: • • • • • • Vit D Phosphorous Calcium Alkaline phosphatase Bone biopsy Xrays 7 3/2/2017 Xrays • Looser Lines Treatment • Correct the Vitamin D deficiency • Treat the pain • Ortho referral for fracture care • Will need treatment for life Renal Osteodystrophy • Spectrum of disease in chronic renal patients characterized by bone mineralization deficiency • Seen mostly in dialysis patients • Chronic renal disease is characterized by significantly high phosphorus and parathyroid levels • In a patient with kidney failure, the kidneys stop making calcitriol, a form of vitamin D. The body then can't absorb calcium from food and starts removing it from the bones. Increase in phosphorous and alkaline phosphatase Orthopaedic Issues Sign and Symptoms • Weakness • Bone pain • Pathological fractures • Skeletal deformities • Symptoms of hypocalcemia • • • • • Abdominal pain Muscle cramps Dyspnea Seizures Mental status changes X-rays: Rugger Jersey • Fractures • Joint sepsis / arthritis • Avascular necrosis (Transplants) • Bone Biopsy 8 3/2/2017 X-rays Looser zone Hip Fractures Bilateral stress fx of femoral necks Treatment Hip fixation • Treat the underlying renal disease • Referrals as appropriate Paget’s Disease • Chronic condition of the bone characterized by abnormal bone remodeling (osteoclasts) • Bone formed is abnormal, large, not as dense, brittle, and prone to breakage • Affects most frequently pelvis, spine, and femur, skull • First described by Sir James Paget in 1877 • Also known as Osteitis Deformans Incidence • Age >40 • Men more than women • English/Scottish decent • Family hx • Approximately 1 million with disease 9 3/2/2017 Diagnosis Clinical Features • May be asymptomatic and found incidentally on x-ray or elevated alkaline phosphatase • Symptoms include bone pain, bone deformity, or neurological manifestations • Labs: • Alkaline phosphatase, calcium, phosphorous, PTH, vitamin D, urine markers of collagen breakdown • X-rays: • plain films and bone scan • Hearing loss and enlarging head Xrays Bonescan Treatment Treatment • Bisphosphonates: • • • • Fosamax Actonel Calcitonin Cal citrate with Vit D • Slows progress and helps with pain • Surgery: • Fixation of fractures • Joint replacement • Reduce pressure on nerves Physical therapy for muscle strengthening Assistive devices 10 3/2/2017 Complications • Dependent on site affected • • • • • • • Deafness Vertigo Fractures Bony deformities OA from altered gait and stress Bone cancer (<1%),prognosis is dismal Heart failure from hypervascularity that increases cardiac load Osteoporosis Follow up • Follow up for life • Monitor alkaline phosphatase • Appropriate referrals(Ortho, Neurosurgeon, ENT, Rheumatology Ophthalmology ,Oncologist Osteoporosis • A silent disease until fracture • 2 million fractures are attributed to osteoporosis • 432,000 hospital admissions • 180,000 nursing home admissions • 80% are billed to Medicare • Cost of care is estimated at 25.3 by 2025 • Only 23% of women with osteoporotic fracture over age of 67 were treated for their osteoporosis Osteoporosis • Disease in which the density and quality of bone are reduced, leading to weakness of the skeleton • This weakness leads to fracture Types of Osteoporosis • Postmenopausal osteoporosis • Age associated osteoporosis • Secondary osteoporosis 11 3/2/2017 Osteoporosis • Secondary Osteoporosis • • • • • • • • • Acromegaly Multiple myeloma Addison’s disease Multiple sclerosis Rheumatoid arthritis Anorexia Sarcoidosis COPD Severe liver disease Osteoporosis • Fracture Liaison Lymphoma Thyrotoxicosis leukemia Malabsorption disorders Spinal cord injury • Bone health champion • Identify patients with recent fractures • • Benefits: • • • • Risk Factors • Post menopausal • Alcoholic (more than 3 drinks a day) • Malabsorption disorders • Lifestyle factors • Medications • Spinal cord injury • Transplant patients Dexa Scans It works Saves money Documents high quality care It’s the right thing to do Osteoporosis NOF Recommendations for Dexa • Woman>65 • Man >70 • Fracture after age of 50 • Menopausal with risk factors • Postmenopausal with risk factors • Man 50-69 with risk factors • Height loss of ½ inch in one year or total of 1 ½ from original height Dexa Scan • DEXA: dual energy x-ray absorptiometry (hip and spine) • pDXA: peripheral dexa (wrist or heel) • QCT: quantitative Cat scan 12 3/2/2017 Dexa Scan • T Score Frax Calculator • +1 to -1 : Normal • An online assessment tool developed by University of Sheffield in England in association with WHO • -1 to -2.5: Osteopenia • www.shef.ac.uk/FRAX/tool.jsp • -2.5 to -3.0: Osteoporosis • Calculates 10 year risk of general fracture and 10 year risk of hip fracture • -3.0 and lower: severe osteoporosis Frax Calculator Frax Calculator • Results: • Osteoporotic fracture probability >20% :TREAT • Osteoporotic hip fracture probability >3% : TREAT Diagnosis • Labs: • • • • • • • • CBC CMP PTH TSH Vit D Alkaline phosphate Testosterone in males Bone turnover markers Treatment • Adequate Calcium and Vitamin D • Pharmacological agents • Weight bearing exercises/physical therapy • Smoking and alcohol cessation 13 3/2/2017 Calcium and Vitamin D • Calcium: • Males 51-70: 1000 mg/day • Females 51-70 1200mg/day • All >70: 1200mg/day • Vitamin D: • 600 IU up to age 70 • 800 IU after age 70 Pharmacological Treatment • Bisphosphonates • Rank ligand inhibitor • Anabolic Hormone • Estrogen agonist/antagonist (selective estrogen receptor modulator) • Estrogen hormone therapy • Calcitonin • National Institutes of Health, May 2015 Bisphosphonates • Slows the breakdown of bone (osteoclast) • Fosamax • Boniva • Reclast Indications • Post menopausal women with vertebral compression fx • Post menopausal women with DEXA less than -2.5 • Men with non-traumatic fracture • Paget's • Some children with osteogenesis imperfecta Contraindication • Esophageal disease • Women who are pregnant or who are planning • CKD stage 4 or 5 • Low serum calcium • Osteomalacia • Vit D deficiency ( until corrected) Complications • Jaw osteonecrosis 14 3/2/2017 Complications • Femur fracture Rank Ligand Inhibitor • Targets and binds to rank ligand, inhibiting osteoclast formation Indications • Postmenopausal women with osteoporosis who have failed or intolerant to other treatments • Men with osteoporosis or have failed or intolerant to other treatments Complications • Hypocalcaemia • Severe infections • Osteonecrosis of Jaw • Atypical fractures • Incapacitating bone and muscle pain Forteo Anabolic Agent • Synthetic parathyroid hormone • Only drug that “builds” bones • Daily injection x 2 years • Indicted for men and women with osteoporosis • Contraindicated in Paget’s disease, unexplained elevated alkaline phosphatase, or history of prior radiation of the skeleton 15 3/2/2017 SERM • Selective Estrogen Receptor Modulator • Acts on estrogen receptors • Slows breakdown of bone • Has been shown to help with compression fractures but not hip • Use up to 5 years • Black box warning of DVT and CVD • Stop if surgery scheduled Calcitonin • Hormone produced by thyroid that lowers serum calcium • Inhibits osteoclast activity • Miacalcin nasal spray: man made hormone • Use for post menopausal(at least 5 years), • Paget’s and hypercalcemia • Use caution with Lithium Estrogen • Not widely used for treatment any more • WHI: risk of breast cancer, uterine cancer, stroke, heart attack, DVT and mental decline • Use lowest dose for lowest duration Osteoporosis • Exercise • Consider physical therapy • Can increase bone mass by 1-2% • Weight bearing exercise Questions???? 16
