Conditions of bone mineral density

Conditions of bone mineral density

• Bone mass is regulated by rates of deposition and withdrawal (Fig.

  1.20).

• Osteoporosis

  • Age-related decrease in bone mass

    • Usually associated with estrogen loss in postmenopausal women (Fig. 1.21)

  • A quantitative, not qualitative, defect

    • Mineralization remains normal

  • World Health Organization’s definition

    • Lumbar (L2–L4) density is 2.5 or more standard deviations less than mean peak bone mass of a healthy 25-year-old (T-score).

    • Osteopenia: bone density is 1.0–2.5 standard deviations less than the mean peak bone mass of a healthy 25-year-old.

  • Responsible for more than 1 million fractures per year

    • Fractures of the vertebral body are most common.

    • History of osteoporotic vertebral compression fractures are strongly predictive of subsequent vertebral fracture.

      • After initial vertebral fracture, the risk for a second vertebral fracture is 20%.

    • Vertebral compression fracture is associated with increased mortality rate.

      • Incidence of vertebral compression fractures is higher among men than women.

    • Lifetime risk of fracture in white women after 50 years of age: 75%

    • The risk for hip fracture is 15%–20%.

  • Risk factors (Box 1.2)

  • Cancellous bone is most affected.

  • Clinical features

    • Kyphosis and vertebral fractures

      • Compression fractures of T11–L1 that create anterior wedge-shaped defects or centrally depressed codfish vertebrae

    • Hip fractures

    • Distal radius fractures

  • Type I osteoporosis (postmenopausal)

    • Primarily affects trabecular bone

    • Vertebral and distal radius fractures common

  • Type II osteoporosis (age-related)

    • Patients older than 75 years

    • Affects both trabecular and cortical bone

    • Related to poor calcium absorption

    • Hip and pelvic fractures are common.

  • Laboratory studies

    • Obtained to rule out secondary causes of low bone mass:

      • Vitamin D deficiency, hyperthyroidism, hyperparathyroidism, Cushing syndrome, hematologic disorders, malignancy

    • Complete blood cell count; measurements of serum calcium, phosphorus, 25(OH)D, alkaline phosphatase, liver enzymes, creatinine, and total protein and albumin levels; and measurement of 24-hour urinary calcium excretion

    • Results of these studies are usually unremarkable in osteoporosis.

  • Plain radiographs not helpful unless bone loss exceeds 30%

  • Special studies

    • Single-photon (appendicular) absorptiometry

    • Double-photon (axial) absorptiometry

    • Quantitative computed tomography (CT)

    • Dual-energy x-ray absorptiometry (DEXA)

      • Most accurate with less radiation

  • Biopsy

After tetracycline labeling

To evaluate the severity of osteoporosis and identify osteomalacia

• Histologic changes

  • Thinning trabeculae

  • Decreased osteon size

  • Enlarged haversian and marrow spaces

• Treatment (Fig. 1.22)

  • Physical activity

  • Supplements: 1000–1500 mg calcium plus 400–800 IU of vitamin D per day

    • More effective in type II (age-related) osteoporosis

  • Bisphosphonates

    • Inhibit osteoclastic bone resorption— direct anabolic effect on bone

    • Categorized into two classes on the basis of presence or absence of a nitrogen side group:

      • Nitrogen-containing bisphosphonates—up to 1000-fold more potent in their antiresorptive activity

        • Zoledronic acid (Zometa) and alendronate (Fosamax)

        • Inhibit protein prenylation within the mevalonate pathway, blocking farnesyl pyrophosphate synthase

        • Results in a loss of GTPase formation, which is needed for ruffled border formation and cell survival

      • Non–nitrogen-containing bisphosphonates

        • Metabolized into a nonfunctional ATP analogue, inducing apoptosis

        • Decreases skeletal

          events in multiple myeloma

        • Associated with osteonecrosis of the jaw

    • Orthopaedic implications of bisphosphonate use

      • Spine—reduced rate of spinal fusion in animal model; withholding bisphosphonate is recommended after surgery.

      • Hip and knee—safe for use in cementless hip arthroplasty and cemented knee arthroplasty; may decrease rate of acetabular component subsidence

         

         

        FIG. 1.20 Four

        mechanisms of bone mass regulation.

        From Netter FH: CIBA collection of medical illustrations, vol 8: Musculoskeletal system, part I: Anatomy, physiology and developmental disorders, Basel, Switzerland, 1987, CIBA, p 181.

         

      • Fracture healing—no good data to recommend for or against use; will decrease future fracture risk

  • Denosumab is a monoclonal antibody that targets and inhibits RANKL binding to the RANK receptor, which is found on osteoclasts.

  • Other drugs (e.g., intramuscular calcitonin) may be helpful.

    • Expensive and may cause hypersensitivity reactions

  • Efficacy of bone augmentation with PTH, growth factors, prostaglandin inhibitors, and other therapies remains to be determined.

• Prophylaxis for patients at risk for osteoporosis

  • Diet with adequate calcium intake

  • Weight-bearing exercise program

     

     

    FIG. 1.21 Age-related changes in density and architecture of human trabecular bone from the lumbar spine. With progressive age, there is a quantitative decrease in bone, but the mineralization (qualitative) remains the same.

     

     

    B ox 1 . 2 R i s k F a c t or s for t h e Dev el opmen t of

    O s t eopor os i s

    • White race, female gender, northern European descent (fair skin and hair)

    • Sedentary lifestyle

    • Thinness

    • Smoking

    • Heavy drinking

    • Phenytoin (impairs vitamin D metabolism)

    • Diet low in calcium and vitamin D

    • History of breastfeeding

    • Positive family history of osteoporosis

                 • Premature menopause       

    From Keaveney TM, Hayes WC: Mechanical properties of cortical and trabecular bone, Bone 7:285–344, 1993.

     

     

  • Estrogen therapy evaluation at menopause

Other causes of decreased mineral density

• Idiopathic transient osteoporosis of the hip

  • Uncommon; diagnosis of exclusion

  • Most common during third trimester of pregnancy in women but can occur in men

  • Groin pain, limited ROM, and localized osteopenia without a history of trauma

  • Treatment: analgesics and limited weight bearing

  • Generally self-limiting and tends to resolve spontaneously after 6–8 months

  • Stress fractures may occur.

  • Joint space remains preserved on radiographs.

• Osteomalacia

  • Femoral neck fractures are common.

  • Qualitative defect

  • Defect of mineralization results in a large amount of unmineralized osteoid.

  • Causes:

    • Vitamin D–deficient diet

    • GI disorders

    • Renal osteodystrophy

    • Certain drugs

      • Aluminum-containing phosphate-binding antacids; aluminum deposition in bone prevents mineralization

      • Phenytoin (Dilantin)

         

         

         

        FIG. 1.22 Treatment options for osteoporosis.

        Adapted from Simon SR, editor: Orthopaedic basic science, Rosemont, IL, 1994, American Academy of Orthopaedic Surgeons, p 174.

         

    • Alcoholism

  • Radiographic findings

    • Looser zones (microscopic stress fractures)

    • Other fractures

    • Biconcave vertebral bodies

    • Trefoil pelvis

  • Biopsy (transiliac) required for diagnosis

    • Widened osteoid seams are histologic

      findings.

  • Treatment: usually includes large doses of vitamin D

• Osteoporosis and osteomalacia are compared in Fig. 1.23.

• Scurvy

  • Vitamin C (ascorbic acid) deficiency

  • Produces a decrease in chondroitin sulfate synthesis

    • Leads to defective collagen growth and repair

       

       

       

      FIG. 1.23 Comparison of osteoporosis and osteomalacia.

      From Netter FH: CIBA collection of medical illustrations, vol 8: Musculoskeletal system, part I: Anatomy, physiology and developmental disorders, Basel, Switzerland, 1987, CIBA, p 228.

    • Also leads to impaired intracellular hydroxylation of collagen peptides

  • Clinical features:

    • Fatigue

    • Gum bleeding

    • Ecchymosis

    • Joint effusions

    • Iron deficiency

  • Radiographic findings:

    • May include thin cortices and trabeculae and metaphyseal clefts (corner sign)

  • Laboratory studies: normal results

  • Histologic features

    • Primary trabeculae replaced with granulation tissue

    • Areas of hemorrhage

    • Widening of the zone of provisional calcification in the physis

      • Greatest effect on bone formation in the metaphysis

• Marrow packing disorders

  • Myeloma, leukemia, and other such disorders can cause osteopenia.

• Lead poisoning

  • Results in short stature and reduced bone density

  • Lead alters the chondrocyte response to PTH-related protein and TGF-β.

Increased osteodensity

• Osteopetrosis (marble bone disease)

  • Result of decreased osteoclast (and chondroclast) function: failure of bone resorption

• Osteopoikilosis (spotted bone disease)

  • Islands of deep cortical bone appear within the medullary cavity and the cancellous bone of the long bones

    • Especially in the hands and feet

    • These areas are usually asymptomatic

  • This disease is accompanied by no known incidence of malignant degeneration.

• Paget disease of bone (osteitis deformans)

  • Elevated serum alkaline phosphatase and urinary