• decreased bone density; radiologic term only - gives no description of disease process!!!
• bone loss must exceed ~40% before detectable
• non-specific, many causes: mineral/collagen; hematologic/endocrine; neoplasia; immobilization

• increased bone density; radiologic term only - gives no description of disease process!!!
• may be localized (sclerotic metastases; primary neoplasms; chronic osteomyelitis; callus of a healing fracture; Paget’s disease)
• may be generalized (congenital osteopenia; fluorosis; myelofibrosis; vit D intoxication; Paget’s disease)

• standard histology of bone requires demineralization prior to fixation
• good for overall structure, but any information about mineralization is lost
• histomorphometry - way to study bone and metabolic bone processes
• procedure
• two doses of tetracycline derivative administered ~ 14 days apart (absorbed by mineralizing bone)
• biopsy of transiliac bone Þ fixation, embedding in hard plasitic (metharcylate), slicing
• section can be stained for minerals
• static variables measured directly (osteoid thickness, etc)
• distance between tetracycline labels used like growth rings on a tree to estimate growth rate, other metabolic processes
• indications for bone biopsy: suspected osteomalacia; osteopenia <50 yrs or with altered Ca metabolism; evaluation of treatment; classification of diseases

• primary: usually benign parathyroid adenoma; skeletal abnormalities in 10-15% of primary hyperparathyroid patients
• secondary: rarely severe or prolonged enough for osteitis fibrosa cystica
• renal osteodystrophy: most common cause; complicated by dialysis and potential Al toxicity
• PTH: stimulates osteoblasts, which in turn:
• secrete proteaes that degrade osteoid
• stimulate bone synthesis
• stimulates osteoclasts
• net effect: bone resorption
• progression of histologic features:
• demineralization: Þ excess osteoid; similar to vit D related osteomalacia
• bone resorption: initially subperiosteal and endosteal surfaces, then trabeculae
• osteoblastic activity: stimulated by resorption Þ leads to rapid bone turnover
• intertrabecular fibrous proliferation: microfractures and microhemorrhages (osteitis fibrosa)
• progression: formation of fibrous cysts - only if untreated, so rare (osteitis fibrosa cystica)
• brown tumors: hemosiderin deposits from hemorrhage; represents the end stage in a given area
• progression may vary depending on the area involved

• childhood form of osteomalacia Þ growth plate open; a defect of mineralization
• etiology: classic form is vit D deficiency (rare in US); renal tubule dysfunction most common in US
• skeletal changes:
• rachitic rosary: beading of costochondral joints
• Harrison’s groove: depression of rib-diaphragm junction
• enlarged wrists, ankles, knees (widening of epiphysis and failure of mineralization)
• curvature of long bones (cortex cannot mineralize Þ bones unable to support weight rigidly)
• spinal abnormalities: dorsal kyphosis, scoliosis, lumbar lordosis Þ decreased height
• pseudofractures similar to osteomalacia
• histologic features – affects areas of most rapid growth
• cartilage in growth plate proliferates without typical (mineralization Þ death Þ ossification) progression
• absence of calcified zone of cartilage (needed for vascularization and ossification)
• irregular columns of proliferating cartilage in growth plate (may extend into bone)

• adult form of Rickets Þ growth plate closed; accumulation of osteoid due to mineralization defect
• etiology: decreased vit D due to nutrition, sunlight deficiency, or renal/hepatic disease
• calcium deficiency due to nutrition, malabsorption, or renal loss (ß reabsorption of phosphate and Ca)
• with renal failure: Al deposits from dialysis tubing or antacids coat the bone surface and prevent mineralization
• symptoms: subtle, non-specific (i.e. bone pain; proximal muscle weakness)
• histologic features:
• increased osteoid on surfaces of trabeculae and cortical bone (at least 10% of bone mass is osteoid)
• also osteoid on lining of Haversian canals
• histomorphometry is used to quantitate osteomalacia; tetracycline uptake is patchy and blurred

• common among elderly (rare in young); loss of bone mass Þ fractures
• different forms
• senile: mostly affects men over 70; progressive loss of bone mass dues to aging
• postmenopausal: mostly affects women; drop in estrogen leads to bone resorption
• secondary: due to hyperadrenocorticism; thyrotoxicosis; hypopituitarism, pregnancy; malnutrition, etc
• disuse: immobilization causes net resorption
• histologic feaures: difficult to diagnose on histo alone (bone loss is slow and unremarkable; remaining bone is normal)
• increased osteoclastic activity in postmenopausal and disuse forms
• resorption starts at cortical endosteal surface Þ thinning of cortex, medullary enlargement; trabeculae may thin

• incidence: common in Northern Europeans; usually found incidentally or at autopsy
• sites of involvement: usually in multiple bones (polyostotic - 85%); lumbar spine 70%, pelvis 65%, also femur, skull, tibia
• pathogenesis: evidence of slow viral infection; most likely measels virus
• histologic features: three phases
• resorptive phase: resorption, fibrosis and vascularization of marrow; rarely recognized
• mixed osteoclast/blast phase:; rapid bone turnover (often woven bone); resembles hyperparathyroidism
• burnt out/quiescent phase: increased, haphazard bone formation/resorption; loose, vascularized tissue in marrow spaces
• complications: nerve compression; fractures; arthritis (bone deformaties; accelerated remodeling of bone results in accelerated ossification of cartilage Þ thinning cartilage); heart failure (due to intraosseus a-v shunts); sarcoma (reported in 1-2% of patients)

• incidence
• most common congenital disease of collagen
• heterogeneous group of conditions with mostly unknown biochemical basis
• grouped based on inheritance pattern (autosomal dominant form predominates)
• clinical features (two forms: congenita - severe; tarda - less severe
• short stature; osteopenia
• blue sclerae, poor dentin formation, ligament laxity Þ disease is generalized CT disorder, not just bone
• both quantitative and qualitative differences in the collagen that is produced (osteoblasts and other CT cells)
• histologic features
• disroganization of proliferative and hypertrophic zones in the growth plate
• increased permeation of cartilage by metaphyseal blood vessels

Osteopetrosis – Marble Bone Disease, Albers-Schonberg Disease