Some nonneoplastic bone disorders Ali Al Khader, M.D. Faculty of Medicine Al-Balqa’ Applied University Email: ali.alkhader@bau.edu.jo

Lecture outline Paget disease (osteitis deformans) Rickets & osteomalacia Osteopenia & osteoporosis Osteomyelitis

Paget disease (osteitis deformans) A disorder of increased, but disordered and structurally abnormal bone mass Late adulthood (average age at diagnosis, 70 years) Striking geographic variation…whites (1-2.5% of elderly population) VS Asians 3 phases: an initial osteolytic stage a mixed osteoclastic-osteoblastic stage …ends with a predominance of osteoblastic activity (3) a final quiescent osteosclerotic stage Many affected individuals are asymptomatic

Paget disease, pathogenesis 40% to 50% of cases of familial Paget disease, and 5% to 10% of sporadic cases, harbor mutations in the SQSTM1 gene ...the net effect of these mutations is to increase the activity of NF-κB, which increases osteoclast activity Suggestions that chronic infection of osteoclast precursors by measles or other RNA viruses may play a role in the disease

Paget disease, morphology This jigsaw puzzle-like appearance is produced by unusually prominent cement lines, which join haphazardly oriented units of lamellar bone Osteosclerotic phase …the findings during the other phases are less specific Mosaic pattern of lamellar bone pathognomonic of Paget disease

Paget disease, clinical course Most cases are asymptomatic and are discovered as an incidental radiographic finding Most affected individuals have mild symptoms Monostotic in about 15% of cases and polyostotic in the remainder The axial skeleton or proximal femur is involved in up to 80% of cases Pain localized to the affected bone is common …caused by microfractures or by bone overgrowth that compresses spinal and cranial nerve roots Enlargement of the craniofacial skeleton may produce leontiasis ossea (lion face) and a cranium so heavy that is difficult for the person to hold the head erect

Paget disease, clinical course…cont’d The weakened Pagetic bone may lead to invagination of the skull base (platybasia) and compression of the posterior fossa Weight bearing causes anterior bowing of the femurs and tibiae and distorts the femoral heads, resulting in the development of severe secondary osteoarthritis Chalk stick-type fractures are another frequent complication and usually occur in the long bones of the lower extremities Compression fractures of the spine result in spinal cord injury and the development of kyphosis The hypervascularity of Pagetic bone warms the overlying skin In severe polyostotic disease the increased blood flow acts like an arteriovenous shunt, leading to high-output heart failure or exacerbation of underlying cardiac disease In less than 1% of all individuals with Paget disease, and in 5% to 10% of those with severe polyostotic disease: sarcoma can occur (osteosarcoma, fibrosarcoma)

Rickets & osteomalacia Both are manifestations of vitamin D deficiency or its abnormal metabolism Diets deficient in calcium and vitamin D, but an equally important cause of vitamin D deficiency is limited exposure to sunlight Other, less common causes of rickets and osteomalacia include renal disorders causing decreased synthesis of 1,25-dihydroxyvitamin D, phosphate depletion and malabsorption disorders Impairment of mineralization and a resultant accumulation of unmineralized matrix This is different from osteoporosis, in which the mineral content of the bone is normal and the total bone mass is decreased Rickets refers to the disorder in children…defective deposition of bone in the growth plates & bowing of legs due to formation of poorly mineralized bones Osteomalacia is the adult counterpart…predisposition to fractures, mostly vertebrae & femur neck

Rickets, clinical features

Osteopenia & osteoporosis Osteopenia = decreased bone mass Osteoporosis = osteopenia that is severe enough to significantly increase the risk of fracture Radiographically, osteoporosis is considered bone mass at least 2.5 standard deviations below mean peak bone mass in young adults and osteopenia as 1 to 2.5 standard deviations below the mean The presence of an atraumatic or vertebral compression fracture signifies osteoporosis May be localized (e.g., disuse osteoporosis of a limb) or involving the entire skeleton (metabolic bone disease) The most common forms of osteoporosis are the senile and postmenopausal types

Osteopenia & osteoporosis, pathogenesis Age-related changes in bone cells and matrix (low-turnover osteoporosis) Reduced physical activity Genetic factors…account for only a small fraction of cases Calcium nutritional state Hormonal influences such as menopause (high-turnover osteoporosis)

Osteopenia & osteoporosis, clinical notes Vertebral fractures that frequently occur in the thoracic and lumbar regions are painful …when multiple, can cause significant loss of height and various deformities, including kyphoscoliosis Complications of fractures of the femoral neck, pelvis, or spine, such as pulmonary embolism and pneumonia, are frequent

Osteopenia & osteoporosis, diagnostic techniques Special radiology techniques are used

Osteomyelitis = infection of bone + bone marrow Part of systemic infection or (most likely) solitary All types or microorganisms, but infections caused by certain pyogenic bacteria and mycobacteria are the most common

Osteomyelitis, pyogenic osteomyelitis Almost always bacterial Routes of bacteria to the bone: 1-hematogenously 2-direct extension 3-direct implantation In healthy children, mostly hematogenously and may be from trivial mucosal injury In adults, more to be from open fractures, surgical procedures, and diabetic infections of the feet

Pyogenic osteomyelitis, causative agents S. aureus is the most common In patients with UTI or IV drug abusers: -E. coli -Pseudomonas -Klebsiella In the setting of direct spread or inoculation of organisms during surgery or into open fractures: mixed organisms In the neonatal period: -Haemophilus influenzae -Group B streptococci Salmonella osteomyelitis is especially associated with sickle cell disease patients We are talking about culture-positive cases …remember that in 50% of the cases, nor organism can be isolated

Pyogenic osteomyelitis, morphology Acute, subacute, or chronic Acute: necrosis of bone and bone marrow tissue + neutrophils Dead bone = sequestrum Rupture of the periosteum leads to a soft tissue abscess which can channel to the skin as a draining sinus In infants, but uncommonly in adults, epiphyseal infection spreads through the articular surface or along capsular and tendoligamentous insertions into a joint, producing septic or suppurative arthritis, which can cause destruction of the articular cartilage and permanent disability.

Pyogenic osteomyelitis, morphology…cont’d After the first week, chronic inflammatory cells predominate …these induce osteoclastic activity and reactive bone formation …this shell of reactive bone around the infected dead part = involucrum What is Brodie abscess? What is sclerosing osteomyelitis of Garré?

Pyogenic osteomyelitis, clinical notes Acute systemic illness with malaise, fever, chills, leukocytosis, and marked-to-intense throbbing pain over the affected region In other instances, the presentation is subtle, with only unexplained fever (most often in infants) or localized pain (most often in adults) A characteristic radiographic findings of a lytic focus of bone destruction surrounded by a zone of sclerosis Blood culture, bone biopsy and culture Combination of antibiotics and surgical drainage are the main therapies 5-25%: transform into chronic osteomyelitis

Complications of chronic osteomyelitis Pathologic fracture Secondary amyloidosis Endocarditis Sepsis Squamous cell carcinoma in the draining sinus tracts Sarcoma in the infected bone

Mycobacterial osteomyelitis 1% to 3% of individuals with pulmonary or extrapulmonary tuberculosis Usually from a focus of active visceral disease during the initial stages of primary infection Typically, affected individuals present with localized pain, low-grade fevers, chills, and weight loss Infection is usually solitary except in immunocompromised individuals The histologic findings, namely caseous necrosis and granulomas More destructive and resistant to control than pyogenic osteomyelitis What is Pott disease??

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