As some terms have vague or even different meanings in the medical literature, the intended meaning of some terms in this article are listed below. (*: The scientifically correct meaning in 2000 AD.)
architecture: the size, shape, and orientation of a bone, the amounts of bone tissue in it, and the arrangement of that tissue in anatomical space.
BMU: the Basic Multicellular Unit of bone remodeling (Jee, 1989)*. In 3 or more months and in a stereotyped, biologically-coupled Activation → Resorption → Formation or “ARF” sequence, it turns over ≈ 0.05 mm3 of bone. The resulting new packet of bone was called a bone structural unit (BSU) by Jaworski (1984). When a BMU makes less bone than it resorbs, that “disuse mode” tends to remove bone permanently, but only for bone next to or close to marrow. When it resorbs and makes equal amounts of bone, that “conservation mode” turns bone over without net gains or losses. Completed BMUs do not seem to make more bone than they resorb so they do not increase bone “mass.” Healthy adult humans may create and complete about 3 million BMUs annually, but in disease and other circumstances that can change more than five times (Frost, 1995).
bone “density”: since the true physical density of bone as a material varies little with age, sex, and species, “density” as absorptiometrists use the term only provides an estimate of the amount of bone in the path of one or more X-ray beams as a bone-mineral equivalent (here one can assume gamma rays and X-rays are the same). While many still think otherwise, true bone density is normal in most osteoporoses and osteopenias (Seeman, 1997). When in quotes in this article, “density” has its meaning in absorptiometry.
bone “mass”: the amount of bone tissue in a bone or skeleton, preferably viewed as a volume minus the volume of the soft tissues in the marrow cavity. In absorptiometry, it does not mean mass as used in physics. When in quotes in this article, it has the absorptiometric meaning.
DEXA: dual energy X-ray absorptiometry. Often also written as “DXA.”
disuse: bones need some criterion to recognize this. When a bone's peak strains down-shift into or below the remodeling threshold region in Figure 3, for that bone that would signal the existence of disuse, no matter how small or big the bone (Frost, 2000a). In such situations, disuse-mode remodeling usually removes bone next to marrow. “Disuse” would be the relationship between a bone's strength and the size of its usual peak loads and the strains they cause. The relationship between those strains and the remodeling threshold would provide a natural criterion for “recognizing” disuse.
disuse-pattern osteopenia: as a steady state, an osteopenia in which endocortical bone loss expanded the marrow cavity, loss of trabecular bone reduced its amount, cortical porosity remains essentially normal, and outside bone diameter does not decrease, or may even increase a bit. The reduced outside bone diameter in some children's osteopenias usually reflects failure of modeling to increase it instead of an effect of periosteal bone loss. In steady-state osteopenias, surface-referent bone tissue dynamics tend to be normal for the subject's age (Recker, 1983).
drifts: see “modeling” below, and Figure 1.
effector cells: here, differentiated osteoblasts and osteoclasts but not their precursor or other cells. The effector cells directly make or resorb bone, so by that definition osteocytes would not be effector cells.
mechanical competence: the state in which bones endure voluntary physical activities for life without developing spontaneous fractures. Sometimes called “biomechanical competence.” The antonym, “mechanical incompetence,” means the state in which voluntary physical activities (not injuries) do cause spontaneous fractures; modeling and/or remodeling disorders would usually cause it.
microdamage: microscopic physical damage in a structural material due to materials fatigue (Martin et al., 1989)*. To increase the fatigue life of inanimate structures, engineers usually add more structural material. But skeletons can detect and repair limited amounts of fatigue damage to keep it from accumulating, so they only need enough strength to keep strains below the level that could cause larger amounts. Presumably they could carry loads that cause smaller amounts indefinitely.
microdamage threshold: the strain range above which new microdamage begins to escape repair and accumulate (MESp in Fig. 3). It seems to center near 3,000 microstrain, which corresponds to a stress of about 60 megapascals. Pattin et al. (1996) found that as the loads that originally cause strains in the 2,000 microstrain range only double to cause 4,000 microstrain, the resulting fatigue damage increases over 500 times.
modeling: the biologic processes that produce functionally purposeful sizes, shapes and organization to all skeletal organs (Jee, 1989)*. Mostly independent resorption and formation modeling drifts do it in bones. Normally it fits bones to their voluntary mechanical usage to keep that usage from breaking them. That is done by making a bone strong enough to keep its typical peak strains from exceeding bone's modeling threshold.
modeling threshold: the genetically-determined Minimum Effective Strain range (or equivalent Stimulus; MESm in Fig. 3) for mechanically controlled bone modeling. Where strains exceed it modeling turns on; where strains stay below it modeling turns off. It seems to center near 1,000 microstrain in most young adults, which corresponds to a stress of about 20 megapascals (Table 4).
muscle strength: the maximum momentary contractile force exerted by a muscle can be expressed in Newtons or kiloponds (the attraction of earth's gravity for a mass of one kilogram) (Dickinson et al., 2000; Murray et al., 1980)*. Or muscle strength can be measured as the peak torque in Newton-meters produced by muscle forces across joints like the hip, elbow, knee, and fingers. That differs from endurance, which concerns how long and often submaximal muscle forces can be exerted, as in marathon running*. It differs from mechanical work or energy, which can be expressed in Newton-meters, Joules, or kilowatt-hours*. It differs from muscle power, which concerns how rapidly mechanical work is done and is usually expressed in Newton-meters/sec, Joules/sec, or watts (one Joule/sec = one watt)*. Since bones seem to adapt their strength and stiffness to the typical peak momentary loads they carry, accounting for these distinctions can minimize errors in interpreting and discussing mechanical usage effects on bone strength and “mass.”
osteopenia: here, less whole-bone strength than usual for most healthy people of the same age, height, weight, sex, and race. Also less bone strength than before in the same person. It need not represent a disease nor stem from an intrinsic bone disorder. Affected bones would break more easily. In clinical work, probably the commonest cause of an osteopenia is chronic muscle weakness. But it is currently and usually expressed in terms of reduced bone “mass” as evaluated by DEXA.
osteoporosis: defining this was debated for decades (Nordin, 1987; Urist, 1960). The currently accepted 1994 WHO “standard” for diagnosing an “osteoporosis” consisted of a bone mineral “density” or content over 2.5 standard deviations below the applicable norm (Kanis, 1994). Some suggested an “osteopenia” consists of a reduction in bone “mass” between 1.0 and 2.4 standard deviations below the applicable norm. That idea does not depend on the osteopenia's pathogenesis, yet effective treatment should depend on it. Reviews published after 1985 show many authors find the “Type I, Type II” terms confusing (Riggs et al., 1998). The pathogenetically-based terms in Part III of this text would supplement older ones. In this text, without quotes the term signifies any osteopenia in which voluntary activities (not trauma) cause spontaneous fractures. When in quotes, it would have the above absorptiometric meaning,
remodeling: turnover of bone in small packets by BMUs (Jee, 1989)*. Pre-1964 literature did not distinguish it from modeling and lumped them together as “remodeling.” While drifts and BMUs seem to create and use the same kinds of osteoblasts and osteoclasts to do their work, in different parts of the same bone at the same time the ‘blasts and ’clasts in drifts and BMUs can even respond oppositely to the same stimulus (Chen et al., 1995; Yeh et al., 1995). Since locally increased remodeling increases local bone formation, scintigrams (“bone scans”) usually show increased local uptake of the bone-seeking radioactive tracer, usually technetium.
remodeling space: increased BMU creations also increase the number of temporary holes in a bone and excavations on its surfaces. That causes a temporary bone loss called the remodeling space. It is temporary because when BMU creations return to normal, the existing holes refill with bone (because of the ARF sequence in BMUs) (Parfitt, 1980). Since increased bone formation accompanies increased remodeling and an increased remodeling space, that can help bone scans (scintograms) with radioactive bone-seeking agents to locate skeletal pathology when ordinary X-rays appear normal (Jergensen et al., 1990).
remodeling threshold: the genetically-determined Minimum Effective Strain range (or equivalent Stimulus; MESr in Fig. 3) that helps to control the switching of BMU-based remodeling between its conservation and disuse modes. When strains exceed it, completed BMUs begin to make and resorb equal amounts of bone to provide conservation-mode remodeling. When strains stay below it, completed BMUs next to marrow make less bone than they resorb to provide the disuse-mode remodeling that mainly affects trabecular and endocortical bone. This threshold may center near 50–100 microstrain, which would correspond to a tension or compression stress of ≈ 1–2 megapascals. One might also define the threshold as the region just to the left of the “adapted window” in Figure 3, which could put the corresponding threshold strain range in the 400–600 microstrain region.
resorption: different meanings of this term in the literature cause some confusion. Some authors use it to mean net bone loss, and in that sense discuss “antiresorption agents.” While often called antiresorption agents, estrogen and bisphosphonates really depress BMU creations (Fleisch, 1995; Jee, 1995). At first, that decreases global resorption, but due to the ARF sequence in the BMU, an equal decrease in global bone formation usually and eventually follows, so these are really “antiremodeling agents.” This text uses resorption to mean bone resorption by osteoclasts. It refers to net losses of bone as such and separately.
strain: the deformation or change in dimensions and/or shape caused by a load on any structure or structural material*. It includes stretching, shortening, twisting, and/or bending. Loads always cause strains, even if very small ones, and three kinds occur: compression, tension, and shear. Biomechanicians can express strain in microstrain units (millionths of a 100% strain), where 1,000 microstrain in compression would shorten a bone by 0.1% of its original length, 10,000 microstrain would shorten it by 1% of that length, and 100,000 microstrain would shorten it by 10% of that length (and break it). Strain emerges as an important signalling mechanism in controlling a skeleton's structural adaptations to its mechanical usage.
strength: the load or strain that, when applied once, usually fractures a bone (also the “ultimate strength”; Fx in Fig. 3)*. Normal lamellar bone's fracture strength expressed as a strain is a range centered near 25,000 microstrain (somewhat lower in adults and higher in rapidly growing mammals). That corresponds to a change from 100% of its original length to 97.5% of that length under compression, or to 102.5% of it under tension (Table 4).
strength-safety factor: when defined as how much stronger a bone is than needed to carry the typical largest voluntary loads on it, this factor would equal the ultimate strength divided by the modeling threshold when both are expressed as stresses. From Table 4 and in young adults, that would equal 120 mpa ÷ 20 mpa = 6. Since the modeling threshold determines the largest allowed bone strain or stress, when that threshold lies below the ultimate strength it creates the safety factor. Bones cannot foresee and adapt their strength to future injuries, so they must adapt to past and present voluntary physical activities instead, whether the activities are subnormal, normal, or supranormal.
“supranormal” exercise: here, high-force muscular activities that cause the largest momentary voluntary loads on bones. Examples include weight lifting and high-acceleration sports like soccer and US-style football.
typical peak strains: visualize a histogram that plots the sizes of a bone's strains (or loads) on the vertical axis, and on the horizontal axis the number of times dynamic strains of a given size occurred during, say, a week. The strains large enough to turn modeling on would be the largest ones in that histogram, but would comprise fewer than 0.01% of all strain events in that week. For example, each systolic pulse in the marrow cavity is a loading event on a hollow bone like the femur. In a week it would carry over 725,000 corresponding strains, of which only ≈ 50 from peak muscle forces might be large enough to reach or exceed bone's modeling threshold. The bone would adapt its strength and “mass” to those ≈ 50 events and pay little attention to all others. While some controversy affected this feature, the different bone strengths of long distance runners and weight lifters strongly suggest it is true. It would also be an obligatory effect of a modeling threshold's existence, which led me to infer that threshold's existence before in vivo strain studies verified its existence (Frost, 1964).