Synopsis of Orthopaedic Trauma Management. Brian H. Mullis

HA, Wang X, Moore TA, Wilber JH, Como JJ. Timing of orthopaedic surgery in multiple trauma patients: development of a protocol for early appropriate care. J Orthop Trauma 2013;27(10):543–551

      10 Osteoporosis

       David Donohue and Hassan R. Mir

      Introduction

      Osteoporosis is defined as decrease in bone mass and microarchitecture deterioration ultimately leading to a decrease in bone strength and increased risk of fragility fracture. In the United States, 44 million women and men over 50 years of age are either osteoporotic or osteopenic. Throughout the world, 200 million people are osteoporotic. Fragility fractures of the hip, spine, wrist, and pelvis are associated with significant morbidity and mortality, including 20% mortality following hip fracture. There are high costs associated with treatment and recovery from fragility fractures, with an estimated 19 billion dollars in the United States alone.

      Keywords: osteoporosis, fragility fractures, dual energy X-ray absorptiometry (DEXA), bisphosphonates, calcium, vitamin D

      I. Bone Health

      A. Peak bone mass is achieved in early adulthood (early 20s).

      1. Most important risk factor for osteoporosis is low peak bone mass.

      2. Determined by genetics, physical activity, nutrition, and hormonal balance.

      3. Bone mass begins to decrease in the fourth decade of life due to shift of balance to favor bone resorption.

      II. Bone Physiology

      The skeletal system serves two primary functions: mechanical support to the body and mineral homeostasis. Bone formation is coupled with bone resorption to allow reorganization of bony architecture along lines of stress (Wolff’s law; Chapter 1, Physiology of Fracture Healing, ▶Fig. 1.5) thus providing maximal structural support, and to allow liberation and sequestration of the body’s calcium stores.

      A. The remodeling process depends on the function of three cell types.

      1. Osteoblasts—form bone

      a. Secrete type I collagen in addition to noncollagenous proteins that compose osteoid. Type I collagen forms a triple helix (two α1 chains and one α2 chain) arranged in parallel array with gaps between the ends of the molecule (hole zones) and in the parallel spaces (pores). Mineralization of bone (inorganic phase composed of calcium hydroxyapatite) begins in the hole zones.

      b. Maturation is induced by transcription factors Runx₂ and Osterix.

      c. Secrete receptor activator of nuclear factor- κβ ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) which stimulate osteoclast differentiation.

      2. Osteoclasts—break down bone

      a. Monocyte lineage, differentiate after expression of transcription factor PU.1 which leads to expression of M-CSF receptor and RANK.

      b. RANKL, a cytokine secreted by osteoblasts and member of the TNFα family, is the most critical and terminal factor necessary for the differentiation of the osteoclast from the monocytic precursor cells.

      c. Form ruffled border (increased surface area) and bind to α_vβ₃ integrin to create a sealed pocket into which carbonic acid (breaks down mineralized bone) and cathepsin K (breaks down organic matrix of bone) are pumped.

      d. Balanced by secretion of osteoprotegerin (OPG) by the osteoblast. This is a “decoy receptor” for RANKL. Denosumab (antiresorptive medication) is a synthetic version OPG.

      e. Amount of bone resorbed depends on the number of mature osteoclasts, their lifespan, and activity level. While the former is governed by the ratio of RANKL/OPG, the latter two are increased in the presence of inflammatory cytokines (IL-1, IL-6, M-CSF, TNFα).

      f. Secrete bone morphogenetic protein (BMP) to stimulate differentiation of osteoblasts.

      3. Osteocytes—derived from osteoblasts that become encapsulated in the bone matrix they secreted.

      a. Most abundant cells in bone (95%).

      b. Cytoplasmic processes extend to adjacent cells through canaliculi and serve as the “neural network” of the bone.

      i. Facilitate mechanical signal transduction via the piezoelectric effect, and mediate the remodeling process such that more bone is deposited in areas where greater force is detected (again, Wolff’s law).

      B. Imbalance in the remodeling process in favor of bone resporption leads to decrease in bone mineral density and trabecular microarchitecture. This results in weakening of the material and structural properties of bone, and thus increase in the risk of fracture.

      III. Types of Osteoporosis

      A. Primary

      1. Type 1: Postmenopausal—decrease in net bone formation.

      a. Due to low estrogen levels (low 17β estradiol results in increased levels of circulating pro-inflammatory cytokines).

      b. Bone loss is rapid immediately following menopause and tapers as time goes on (less trabecular architecture to resorb).

      2. Type II: Senile—age-related decline in osteoblast function.

      a. Usually seen in patients over the age of 70 years.

      b. Affects both trabecular and cortical bone.

      B. Secondary (Type III)—results from medical illness, medication or lifestyle derangement (see risk factors below):

      1. The list is quite inclusive, and the mechanisms by which each condition causes osteoporosis are often multifactorial and overlapping.

      2. These diseases and their sequelae either result in an impediment to achievement of peak bone mass during youth or increase the rate of bone loss during the remodeling process.

      IV. Nonmodifiable Risk Factors for Osteoporosis

      A. Female gender

      1. Women have lower peak bone mass and postmenopausal decrease in estrogen.

      2. Lower risk in elderly men due to peripheral aromatization of testosterone to estrogen. In general, men have greater bone mineral density, larger bone cross-sectional area, and cortical thickness.

      B. Increased age

      1. 90% of fragility fractures occur in patients > 50 years old.

      C. Small/thin body size

      1. Increased body weight and body mass index (BMI) are associated with decreased rates of osteoporosis, most likely due to increased mechanical load and peripheral conversion of androgens to estrogen in adipose tissue.

      2. BMI < 20 (thin frame) is associated with increased risk of fracture.

      D. Ethnicity: Caucasian and Asian women are at the highest risk due to lower peak bone mass.

      E. Family history of fragility fracture.

      V. Modifiable Risk Factors for Osteoporosis

      A. Estrogen deficiency—postmenopausal, hypogonadism, low caloric intake, excessive exercise.

      B. Medical conditions

      1. Genetic: Ehlers–Danlos syndrome, Marfan’s syndrome, Gaucher’s disease, hemochromatosis,