Snapshot A 65-year-old man presents with worsening left-sided hearing loss and mild headache. He reported that his symptoms began a few months prior to presentation. He denies starting any new medications but has noticed he can no longer fit the hat he has owned for many years. Physical examination is unremarkable. Laboratory testing is notable for an elevated serum alkaline phosphatase. A radiograph of the skull is shown. Introduction Clinical definition a progressive metabolic bone disorder of abnormal bone remodeling there is excessive bone resorption and formation resulting in login to view 1 more bullet Background adult bone constantly undergoes bone remodeling and is accomplished by osteoclasts login to view 2 more bullets osteocytes login to view 3 more bullets osteoblasts login to view 3 more bullets bone matrix has two histological forms woven login to view 3 more bullets lamellar login to view 1 more bullet Pathogenesis genetic and environmental factors may be involved increased multinucleated osteoclastic and osteoblastic activity leads to a high bone remodeling rate, leading to abnormal bone architecture phases lytic phase login to view 1 more bullet mixed phase login to view 1 more bullet sclerotic phase login to view 1 more bullet all three phases may co-exist in the same bone Associated findings neurologic nerve root compression hearing loss spinal stenosis orthopedic pathologic fractures secondary osteoarthritis oncologic osteosarcoma cardiovascular high-output heart failure labs normal serum phosphate, calcium, and parathyroid hormone elevated alkaline phosphatase histology mosaic pattern of lamellar bone with prominent cement lines Normal Biology and Anatomy adult bone constantly undergoes bone remodeling and is accomplished by osteoclasts contains receptor activator for NF-κB (RANK) transmembrane receptors which login to view 1 more bullet osteocytes secrete growth factors to regulate bone formation login to view 1 more bullet contains RANKL osteoblasts contain RANKL and osteoprotegerin (OPG) login to view 1 more bullet functions in bone formation bone matrix has two histological forms woven has less structural integrity seen in fetal development and fracture repair always considered abnormal in adults lamellar has more structural integrity Laboratory Abnormalities in Select Bone Disorders Etiology Serum Phosphate Serum Calcium Serum Alkaline Phosphatase Parathyroid Hormone Osteomalacia/rickets Decreased Decreased Increased Increased Osteoporosis Normal Normal Normal Normal Osteopetrosis Normal Normal or decreased Normal Normal Paget disease of bone Normal Normal Elevated Normal Osteitis fibrosa cystica Primaryhyperparathyroidism decreased Secondaryhyperparathyroidism increased Primaryhyperparathyroidism increased Secondaryhyperparathyroidism decreased Primary and secondary hyperparathyroidism increased Primary and secondary hyperparathyroidism increased Hypervitaminosis D Increased Increased Normal Decreased Presentation Symptoms usually asymptomatic bone and/or joint pain bone deformity bowing deformity hearing loss with skull involvement that lead to narrowing of the auditory foramen Physical exam typically unremarkable Treatment Medical bisphosphonates mechanism of action login to view 2 more bullets