Bone multicellular units

- Discussion:
    - generalized pathologic processes in bone can be best understood by understanding how these processes alter the normal sequence of 
          bone remodeling as described in the previous chapter;
    - bone remodeling occurs in local groups of osteoblasts and osteoclasts called bone multicellular units (BMU);
    - each unit is organized into "cutting cone" of osteoclasts reabsorbing bone followed by trail of osteoblasts reforming the bone to fill defect 
          left by osteoclasts;
          - end product is a new osteon;
    - each BMU has a finite lifetime, so new units are continuously forming as old units are finishing;
    - in normal bone, number of BMUs, bone resorption rate, and bone formation rate are all relatively constant;
    - for this reason a steady-state situation develops such that the total amount of bone "missing" due to bone remodeling at any one time is 
          fairly constant;
    - any changes in the number of BMUs, resorption rate, or formation rate will alter this steady-state situation;
    - in adult, bone removed by a BMU is not 100% restored, & small amount of bone is permanently lost;
    - this gradual bone loss (failure to completely reform bone within each BMU) is a normal phenomenon in humans and accounts for gradual 
          loss of bone with age;
    - pathologic conditions in bone may increase the amount of irreversible bone loss by either increasing the total number of BMUs or by 
          increasing the amount of irreversible bone loss in each BMU;
    - increases in irreversible bone loss per BMU can result from:
          - overactivity of osteoclasts so that more bone is resorbed than "normal" osteoblasts can replace;
    - decreased capacity of osteoblasts to reform "missing" bone although resorption may be normal;
          - irreversible bone loss occurs both in cortical & trabecular bone;
    - theoretically, all cortical bone resorbed could be replaced by osteoblasts, and in trabecular bone >100% of bone removed could be 
          replaced by decreasing marrow "space;"
          - however, in nl adult, this degree of replacement does not occur;
    - if greater bone formation than bone resorption could be induced, the treatment of osteopenic bone conditions would be greatly enhanced;
          - permanent increase in bone mass does not normally occur in adult, except possibly in instances of periosteal bone formation owing to 
    - leading cause of metabolic bone disease is increase in number of BMUs;
    - there are many different types of stimuli that lead to this increase, best studied being parathyroid hormone;
    - in mild hyperparathyroidism the number of BMUs is increased, but rates of bone resorption and formation in each BMU are unaffected
           and remain well matched;
          - amount of irreversible bone loss is, therefore, relatively small;
          - in some situations, such as severe hyperparathyroidism, increase in total bone resorption can be so great that bone formation cannot 
                 keep pace, and large quantities of bone can be lost;
    - metabolic bone diseases characterized by an increase in the amount of irreversible bone loss within each BMU can be produced by 
          alteration in rate of bone resorption, rate of bone formation, or both;
    - mismatch between the rates of formation and reabsorption is critical factor leading to bone loss;
    - in high turnover osteopenia both rates are increased;
    - formation simply does not keep pace with resorption;
    - most patients with postmenopausal osteoporosis have a low turnover osteopenia;
    - in this situation, rate of resorption is generally unchanged, but for unknown reasons, the rate of formation is decreased;

- Biopsy:
    - there are many possible combinations of abnormalities in bone-remodeling dynamics that could cause changes in total bone mass;
    - to understand or treat metabolic bone diseases, it is important to determine which abnormalities in the BMU are present;
    - this is best done by histomorphometric analysis of a bone biopsy after labeling of the bone w/tetracycline, which serves as a dated 
            fluorescent marker;
    - this technique permits quantification of rates of bone formation, resorption, and number of BMUs

Original Text by Clifford R. Wheeless, III, MD.

Last updated by Data Trace Staff on Tuesday, September 13, 2011 1:30 pm