Osteoporosis Educational Series, Lecture 2of 3: Understanding Bone to Understand Osteoporosis: Pathogenesis and Risk Factors Nahid Rianon, M.D., Dr.P.H. The University of Texas Health Science Center at Houston

Goal and Objectives GOAL: The goal of this presentation is to describe detail mechanism of bone loss and risk of fractures LEARNING OBJECTIVES: At the end of this presentation, attendees will be able to  Explain normal and abnormal state of bone metabolism  Define bone remodeling  Identify risk factors for bone loss  Calculate risk of facture

What percent of adult human bone is made of minerals? a)20% b)65% c)75% d)90% Pre Quiz Question 1 of 5

Which of the following factors stimulate osteoblasts? (Choose one) a)Glucocorticoids and Estrogen b)Thyroxine and Androgen c)Estrogen and Growth Hormone d)Vitamin D and Thyroxine Pre Quiz Question 2 of 5

Which one of the following statements best fits the pathological state of osteoporosis due to age related bone loss? a)Bone formation and resorption are in balance b)Both formation and resorption slows down at the same rate c)Both formation and resorption increases at the same rate d)Bone resorption is greater than bone formation Pre Quiz Question 3 of 5

Which of the following diseases is not considered a risk for developing secondary osteoporosis (when remains untreated) for FRAX calculation tool? a)Diabetes Mellitus type II b)Hypothyroidism c)Diabetes Mellitus type I d)Osteogenesis Imperfecta in adults Pre Quiz Question 4 of 5

Pre Quiz Question 5 of 5 In humans, trabecular bone volume is larger than cortical bone volume? a) True b) False

Function  Mechanical  Weight bearing  Protection for soft organs  Attachment for muscles  Mineral reservoir  Calcium  Phosphorus Why Do We Need Strong Bones:

Overall  Organic Matrix  10% of adult bone  Primarily protein collagen -provides flexibility  Mineral Component  65% of adult bone  Hydroxyapatite - insoluble salts of calcium (99%) & phosphorus (85%)  Very little Mg, Na & HCO 3  Water  25% of adult bone Bone Structure

Cellular  Osteoblasts  Critical to bone formation  Osteoclasts  Reabsorb bone  Osteocytes  Exact role is still under investigation Bone Structure Osteoblasts Osteoclasts Osteocytes

Types of boneForces on bone Trabecular  20% of skeletal mass  Greater surface area than cortical  Provides supporting strength to the ends of weight-bearing bones Cortical  80% of skeletal mass  Solid outside shaft of long bones Compressive stress  From body weight pushing the bone down Tensile stresses  From muscles, pulling the bone apart Bone Structure

Trabecular and Cortical Bones Trabecular bone Cortical bone Femur with loss of mineral and microstructure Healthy femur Tensile Comprehensive Mineral loss

Physiology- Normal State Bone Marrow Progenitors Osteoblast PrecursorOsteoclast Precursor Glucocorticoids Estrogen Calcitonin Estrogen Androgens GH/IGF-1 Thyroxine Vitamin A Osteoblast New Bone Formation Bone Resorption Osteoclast Osteocyte 1,25 OHD PTH + _ _ *Find out if this is 1,25 (OH)2D +

Pathogenesis Of Osteoporosis - Bone Remodeling Normal Bone Remodeling Sequence Resorption = Formation No change in bone mass LEGEND: LC = Lining Cells CL = Cement Line OS = Osteoid BRU = Bone Remodeling Unit Osteoclast Precursor Osteoclast Osteoblast Precursors Osteoblast Mononuclear Cells

High bone turnover state Unbalanced remodeling Osteoporosis Basic Pathology Normal Bone Structure Osteoporotic Bone Structure

Resorption > Formation Net bone loss Unbalanced Remodeling & Osteoporosis Influencers: Inadequate calcium or vitamin D Menopause Aging Medications or diseases

 Increasing age  Female gender  Early menopause  Low body weight  Previous fracture  Family history  Low calcium intake  Low vitamin D  Alcohol  Smoking  Physical inactivity  High caffeine intake  Drug use- steroid  White or Asian race Osteoporosis Risk Factors

FRAX Calculator

 Age (40-90), gender, height & weight  Previous fracture  Hip fracture in parents  Current smoking  Alcohol  Glucocorticoids (oral) ≥ 3 dose 5mg daily or more  or equivalent doses of other glucocorticoids  Rheumatoid arthritis  Secondary osteoporosis  DM-I, OI in adults,  Untreated hyper or hypothyroidism,  Premature menopause (< 45 yrs),  Chronic malnutrition or malabsorption &  Chronic liver disease  Bone mineral density (BMD) FRAX Risk Factors

Post Quiz Question 1 of 5 What percent of adult human bone is made of minerals? a)20% b)65% c)75% d)90%

Post Quiz Question 2 of 5 Which of the following factors stimulate osteoblasts? (Choose one) a)Glucocorticoids and Estrogen b)Thyroxine and Androgen c)Estrogen and Growth Hormone d)Vitamin D and Thyroxine

Post Quiz Question 3 of 5 Which one of the following statements best fits the pathological state of osteoporosis due to age related bone loss? a)Bone formation and resorption are in balance b)Both formation and resorption slows down at the same rate c)Both formation and resorption increases at the same rate d)Bone resorption is greater than bone formation

Post Quiz Question 4 of 5 Which of the following diseases is not considered a risk for developing secondary osteoporosis (when remains untreated) for FRAX calculation tool? a)Diabetes Mellitus type II b)Hypothyroidism c)Diabetes Mellitus type I d)Osteogenesis Imperfecta in adults

In humans, trabecular bone volume is larger than cortical bone volume? a) True b) False Post Quiz Question 5 of 5

Questions? Thank You

Reference American Society for Bone and Mineral Research WHO Fracture Risk Assessment Tool (FRAX)

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