Nonneoplastic Bone Disease

Non-neoplastic bone diseases Rickets and Osteomalacia  Rickets and osteomalacia are disorders characterized by a defect in matrix mineralization, most often related to a lack of vitamin D or some disturbance in its metabolism. The term rickets refers to the disorder in children in which deranged bone growth produces distinctive skeletal deformities. In the adult the disorder is called osteomalacia, because the bone that forms during the remodelling process is inadequately mineralized. This results in osteopenia and predisposition to insufficiency fractures Hyperparathyroidism  Primary hyperparathyroidism results from autonomous hyperplasia or a tumour, usually an adenoma, of the parathyroid gland, whereas secondary hyperparathyroidism is commonly caused by prolonged states of hypocalcaemia resulting in compensatory hypersecretion of PTH. Whatever the basis, the increased PTH concentrations are detected by receptors on osteoblasts, which then release factors that stimulate osteoclast activity. Thus, through a chain of signals, the skeletal manifestations of hyperparathyroidism are caused by unabated osteoclastic bone resorption. Some of the other clinical signs include localised ‘brown tumour’ and generalised osteitis fibrosa cystica Renal osteodystrophy   The term renal osteodystrophy is used to describe collectively all of the skeletal changes of chronic renal disease, including: o increased osteoclastic bone resorption mimicking osteitis fibrosa cystica o delayed matrix mineralization (osteomalacia) o osteoporosis Pathogenesis/mechanism examples: o Decreased phosphate excretion & vitamin D conversion to active from  increased PTH  increased osteoclastic activity & bone resorption o Metabolic acidosis  increased bone reabsorption and de-mineralisation Osteoporosis  Osteoporosis is a disease characterized by porous bones and a reduced bone mass. The associated structural changes predispose the bone to fracture, particularly around the thora-lumbar vertebral level. The disorder may be localized to a certain bone or region, as in disuse osteoporosis of a limb, or may involve the entire skeleton, as a manifestation of a metabolic bone disease  Pathogenesis: o Aging o Reduced osteoblastic activity i.e. bone loss with each resorption/formation cycle o Physical inactivity o Genetics o Calcium nutrional status o Hormonal influences e.g. oetrogen deficiency  increased inflammatory cytokines  increased osteoclast activity Paget disease (Osteitis deformans)  This unique skeletal disease can be divided into three phases; an initial osteolytic stage, followed by a mixed osteoclastic-osteoblastic stage, which ends with a predominance of osteoblastic activity and evolves ultimately into a burnt-out quiescent osteosclerotic stage. The net effect is a gain in bone mass; however, the newly formed bone is disordered and architecturally unsound. The hallmark of this disease is the mosaic pattern of lamellar bone Developmental abnormalities    Achondroplasia involves a mutation of FGFR3, such that it causes inhibited cartilage proliferation and supresses growth. Therefore, this disease is a major cause of dwarfism as the patient often has short proximal limbs and an enlarged head Osteogenesis imperfecta, or brittle bone disease, is a phenotypically diverse disorder caused by deficiencies in the synthesis of type 1 collagen. It is the most common inherited disorder of connective tissue. It principally affects bone, but also impacts other tissues rich in type 1 collagen (joints, eyes, ears, skin, and teeth) Osteopetrosis, also known as marble bone disease and Albers-Schönberg disease, refers to a group of rare genetic diseases that are characterized by reduced bone resorption and diffuse symmetric skeletal sclerosis due to impaired formation or function of osteoclasts. The term osteopetrosis reflects the stone-like quality of the bones; however, the bones are abnormally brittle and fracture easily, like a piece of chalk Osteonecrosis  Infarction of bone and marrow is a relatively common event that can occur in the medullary cavity of the metaphysis or diaphysis and the subchondral region of the epiphysis. Ischemia underlies all forms of bone necrosis, which can occur in the setting of diverse predisposing conditions. In this disease, the cartilage remains viable and necrotic fat cells form in marrow Osteomyelitis   Osteomyelitis denotes inflammation of bone and marrow, and the common use of the term virtually always implies infection Examples: o Pyogenic osteomyelitis is almost always caused by bacteria. Organisms may reach the bone by haematogenous spread, extension from a contiguous site, and direct implantation o Tuberculous osteomyelitis is occurring in developed countries, attributed to the influx of immigrants from countries where tuberculosis is endemic. More destructive than pyogenic