1. Some nonneoplastic bone disorders
Ali Al Khader, M.D.
Faculty of Medicine
Al-Balqa’ Applied University

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

3. 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

4. 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

5. 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

6. 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

7. 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)

8. 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

9. Rickets, clinical features

10. 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

12. 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)

13. 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

14. Osteopenia & osteoporosis, diagnostic techniques
Special radiology techniques are used

15. 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

16. 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

17. 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

18. 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.

19. 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?

20. 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

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

22. 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??

23. Thank You