Harold M. Frost

The Biology of Fracture Healing: An Overview for Clinicians. Part I

The bone healing process normally unites fractures, arthrodeses, osteotomies, and bone grafting operations. The process normally proceeds in successive stages named the fracture, granulation, and modeling/remodeling stages. A separate regional acceleratory phenomenon speeds up each of the other stages. The osteoclast and osteoblast cells that make intercellular substances of each stage do not exist in sufficient numbers to heal the bone at the moment of fracture or operation. They are made by local multicellular mediator mechanisms that contain precursor and supporting cells, capillaries, lymph, and innervation, plus local autocrine and paracrine regulation. Under the influences of local and systemic agents, these mediator mechanisms determine whether new local osteoclasts and osteoblasts will appear, in addition to when, where, how many, what kind, and for how long. Errors in those functions can then lead to several kinds of retarded or otherwise abnormal bone healing that will be discussed in Part II of this work.

On the rat model of human osteopenias and osteoporoses

The idea that rats cannot model human osteopenias errs. The same mechanisms control gains in bone mass (longitudinal bone growth and modeling drifts) and losses (BMU-based remodeling), in young and aged rats and humans. Furthermore, they respond similarly in rats and man to mechanical influences, hormones, drugs and other agents.

Wolff's Law and bone's structural adaptations to mechanical usage: an overview for clinicians

Basic Multicellular Unit-based bone remodeling can lead to the removal or conservation of bone, but cannot add to it. Decreased mechanical usage (MU) and acute disuse result in loss of bone next to marrow; normal and hypervigorous MU result in bone conservation. Bone modeling by resorption and formation drifts can add bone and reshape the trabeculae and cortex to strengthen them but collectively they do not remove bone. Hypervigorous MU turns this modeling on, and its architectural effects then lower typical peak bone strains caused by future loads of the same kind to a threshold range. Decreased and normal MU leave this modeling off. Where typical peak bone strains stay below a 50 microstrain region (the MESr) the largest disuse effects on remodeling occur. Larger strains depress it and make it conserve existing bone. Strains above a 1500 microstrain region (the MESm) tend to turn lamellar bone modeling drifts on. By adding to, reshaping and strengthening bone, those drifts reduce future strains under the same mechanical loads towards that strain region. Strains above a 3000 microstrain region (the MESp) can turn woven bone drifts on to suppress local lamellar drifts but can strengthen bone faster than lamellar drifts can. Such strains also increase bone microdamage and the remodeling that normally repairs it. Those values compare to bones fracture strain of about 25,000 microstrain.

On Our Age-Related Bone Loss: Insights from a New Paradigm

Bone strength and “mass” normally adapt to the largest voluntary loads on bones. The loads come from muscles, not body weight. Bone modeling can increase bone strength and “mass,” bone remodeling can conserve or reduce them, and each can turn ON and OFF in response to its own threshold range of bone strains. During growth, the loads on bones from body weight and muscle forces increase, and modeling correspondingly increases bone strength and “mass.” In young adults those loads usually plateau, so bone strength can “catch up” and modeling can turn OFF. Meanwhile remodeling keeps existing bone. After about 30 years of age, muscle strength usually decreases. In aging adults this would put bones that had adapted to stronger young‐adult muscles into partial disuse and make remodeling begin to reduce their strength and “mass,” as disuse regularly does in experimental situations in other mammals, both growing and adult. Those changes associate strongly with the size of the bone strains caused by the loads on bone. While nonmechanical effects associated with aging should contribute to that age‐related bone loss too, a new skeletal paradigm suggests the above mechanical influences would dominate control of the process in time and anatomical space.

A determinant of bone architecture. The minimum effective strain.

Minimum effective strain (MES), a hypothesis since 1964, has achieved experimental support. The range is about 0.0008-0.002 unit bone surface strain. Strains below the MES apparently do not evoke adaptive architectural bone modeling, but those above it do. As a key property of living lamellar bone and its intermediary organization, MES offers the potential to predict exactly when and where mechanical loads will cause bone architectural adaptations. MES represents a step toward the goal of constructing a specific, predictive, and quantitative theory of the mechanical determinants of skeletal architecture.

Preparation of thin undecalcified bone sections by rapid manual method.

Sections from 3 μ to over 100 μ thick of fresh, unfixed, unembedded, unde-calcified and undehydrated bone are made by grinding 1 to 2 mm slabs of the desired orientation on waterproof carborundum abrasive paper, grit No. 320, 360 or 400. The manner of controlling the section is the crux of the technique. The section is held by wrapping a fresh strip of sandpaper around a 3″ × 1″ slide and accomplishing the grinding on a used piece of paper. The abrasive points on the fresh paper effectively prevent the section from sliding off the slide. The specimen is kept wet with water during the entire procedure. Sections are then stained, and excess surface stain can be ground off in similar fashion. After washing in dilute detergent solution to remove adherent derbis, the section is air dried and mounted in any nonacidifying resinous media. The method is suitable for wood and for fruit pits also.

On the Estrogen–Bone Relationship and Postmenopausal Bone Loss: A New Model

In this model of estrogen effects on bone, a postulated mediator mechanism in marrow would affect modeling and remodeling only of bone next to or close to it. That mediator mechanism could sense estrogen. In response to that hormone, it would let remodeling of bone next to marrow proceed in its conservation mode. This would minimize losses of that bone and tend to prevent an osteopenia. But acute estrogen deficiency would make that mechanism switch remodeling of bone next to marrow to its disuse mode. Meanwhile, conservation‐mode remodeling would continue for haversian and subperiosteal bone. The resulting losses of bone next to marrow would expand marrow cavities, thin cortices, and reduce trabecular bone “mass,” but would not reduce outside bone diameters. That scheme could explain the osteopenia that follows natural or experimental estrogen deficiency in mammalian females. If so, as estrogen secretion rises in girls at puberty they should begin accumulating more bone next to marrow. They do. Also if so, at menopause women should begin to lose that bone. They do. Those effects would exist in addition to known effects of estrogen on existing osteoclasts and osteoblasts.

in Vivo Osteocyte Death

Counts of the percentage of empty osteocyte lacunae were done on fresh, undecalcified bone sections of specimens from forty-five human subjects ranging in age from new-born infancy to eighty-four years. The average figures from arbitrary age groups suggest that an increasing percentage of bone dies with increasing age. At seventy years, 45 per cent of Haversian bone and 75 per cent of extra-Haversian bone have empty lacunae.

Migratory Osteolysis of the Lower Extremities

Excerpt Osteoporosis is most often a generalized disturbance and when confined to a local region usually results from inactivity of the affected part. The main causes for localized osteoporosis (os...

Staining of fresh, Undecalcified, thin Bone Sections

Fresh, undecalcified bone sections can be reproducibly and reliably stained by any of the following procedures: (A) Basic fuchsin, 1% in 30% alcohol, 48 hr, 22°C. (B) AgNO3, 0.033 M, 48 hr, 22°C; washing 48 hr in a large volume of distilled water; exposure to light to develop the color