Biomedical subjects

Harold M Frost

Publications and source records attributed to Harold M Frost.

7 recordsLinked to original sources

PubMed2005

Muscle atrophy and bone loss after 90 days' bed rest and the effects of flywheel resistive exercise and pamidronate: results from the LTBR study.

Muscle atrophy and bone loss pose substantial problems for long-term space flight and in clinical immobilization. We therefore tested the efficacy of flywheel resistive exercise and pamidronate to counteract such losses. Twenty five young healthy males underwent strict bed rest with -6 degrees head-down tilt for 90 days. Subjects were randomized into an exercise group that practiced resistive exercise with a 'flywheel' (FW) device every 2-3 days, a pamidronate group (Pam) that received 60 mg pamidronate i.v. 14 days prior to bed rest and a control group (Ctrl) that received none of these countermeasures. During the study, Ca(++) and protein intake were controlled. Peripheral quantitative computed tomography (pQCT) was used to assess bone mineral content (BMC) and muscle cross sectional area (mCSA) of calf and forearm. Measurements were taken twice during baseline data collection, after 28 and after 89 days bed rest, and after 14 days recovery. On the same days, urinary Pyridinoline excretion and serum levels of alkaline phosphatase, Ca(++) and PTH were measured. Pre-study exercise habits were assessed through the Freiburg questionnaire. Losses in calf mCSA were significantly reduced in FW (Ctrl: -25.6% +/- 2.5% Pam: -25.6% +/- 3.7%, FW: -17.3% +/- 2.7%), but not in the forearm mCSA (Ctrl: -6.4% +/- 4.33%, Pam: -7.7% +/- 4.1%, FW: -7.6% +/- 3.3%). Both diaphyseal and epiphyseal BMC losses of the tibia were mitigated in Pam and FW as compared to Ctrl, although this was significant only at the diaphysis. Inter-individual variability was significantly greater for changes in BMC than in mCSA, and correlation of BMC losses was poor among different locations of the tibia. A significant positive correlation was found between change in tibia epiphyseal BMC and serum cortisol levels. These findings suggest that both countermeasures are only partly effective to preserve BMC (FW and Pam) and mCSA (FW) of the lower leg during bed rest. The partial efficacy of flywheel exercise as well as the bones' response to unloading per se underlines the importance of mechanical stimuli. The huge variability of BMC changes, however, suggests that other factors affect changes in whole-bone strength following acute mechanical disuse.

Adult↗

PubMed2004

A 2003 update of bone physiology and Wolff's Law for clinicians.

By 1892, Julius Wolff and others realized that mechanical loads can affect bone architecture in living beings, but the mechanisms responsible for this effect were unknown, and it had no known clinical applications. In 2003 we know how this effect occurs and some of its applications. Our load-bearing bones (LBBs) include tibias, femurs, humeri, vertebrae, radii, mandibles, maxillae, wrists, hips, etc (so LBBs are not limited to weight-bearing ones). The strength of such bones and their trabeculae would represent their most important physiologic feature but in the special sense of relative to the size of the typical peak voluntary loads on them. The biologic "machinery" that determines whole-bone strength forms a tissue-level negative feedback system called the mechanostat. Two thresholds make a bone's strains determine its strength by switching on and off the biologic mechanisms that increase or decrease its strength. Equally, two thermostats can determine a room's temperature by switching on and off the room's heating and cooling systems. General features show that the largest voluntary loads on LBBs determine most of their strength after birth. These loads come from muscle forces so muscle strength strongly influences the strength of our LBBs. This process affects, in part, the healing of fractures, bone grafts, osteotomies, and arthrodeses; the bone's ability to endure load-bearing joint and dental endoprostheses; why healthy bones are stronger than the minimum needed to keep voluntary loads from breaking them suddenly or from fatigue; some general functions and disorders of bone modeling and basic multicellular unit-based bone remodeling; some limitations of in vitro data and of pharmaceutical actions; and the fact that many bone-active humoral and local agents have permissive roles in a bone's adaptations and healing, instead of forcing them to occur.

Biomechanical Phenomena↗

PubMed2003

Bone's mechanostat: a 2003 update.

The still-evolving mechanostat hypothesis for bones inserts tissue-level realities into the former knowledge gap between bone's organ-level and cell-level realities. It concerns load-bearing bones in postnatal free-living bony vertebrates, physiologic bone loading, and how bones adapt their strength to the mechanical loads on them. Voluntary mechanical usage determines most of the postnatal strength of healthy bones in ways that minimize nontraumatic fractures and create a bone-strength safety factor. The mechanostat hypothesis predicts 32 things that occur, including the gross anatomical bone abnormalities in osteogenesis imperfecta; it distinguishes postnatal situations from baseline conditions at birth; it distinguishes bones that carry typical voluntary loads from bones that have other chief functions; and it distinguishes traumatic from nontraumatic fractures. It provides functional definitions of mechanical bone competence, bone quality, osteopenias, and osteoporoses. It includes permissive hormonal and other effects on bones, a marrow mediator mechanism, some limitations of clinical densitometry, a cause of bone "mass" plateaus during treatment, an "adaptational lag" in some children, and some vibration effects on bones. The mechanostat hypothesis may have analogs in nonosseous skeletal organs as well.

Biomechanical Phenomena↗

PubMed2003

Absorptiometry and "osteoporosis": problems.

"Connecting the dots" between diverse clinical and other matters and an updated bone physiology reveals relationships that could modify some ideas about the roles and uses of absorptiometry in "osteoporosis" work. Herein, absorptiometry means that part of "clinical densitometry" that depends on X-ray absorption by bone and other tissues, thus excluding ultrasound methods and magnetic resonance imaging. The modifications concern, in part, some limitations of bone mineral "density" data, the kinds of physiological information that absorptiometry can and cannot provide, the relative importance of bone "mass" and whole-bone strength, how to define and study bone health and "osteoporosis," and two kinds of "osteoporotic fractures." As those modifications concern important national health care issues, they deserve answers based on hard evidence. Identifying those modifications might help others to evaluate them.

Absorptiometry, Photon↗

PubMed2003

Bone mass, bone strength, muscle-bone interactions, osteopenias and osteoporoses.

Densitometrically, the skeleton is currently conceived as 'a systemically regulated mass of mineralized material that is born, grows, reaches a more or less high peak, and then declines faster or slower as to develop a correspondingly high or low fracture risk'. Alternatively, from a biomechanical point of view, the skeleton can be conceived as 'a biomechanically-regulated structure that can be systemically disturbed (in the cybernetic sense), the strength of which depends on the intrinsic stiffness (material properties) and the spatial distribution (architectural properties) of the mineralized tissue'. The biomechanical feedback system involved (bone 'mechanostat') would not control bone mass to optimize bone strength; it would rather control bone material quality and architecture (through a modulation of bone modeling and remodeling) in order to optimize bone stiffness. The natural stimuli for the bone mechanostat would be the customary strains of bone tissue (sensed by osteocytes) that are induced by gravitational forces and, more importantly, the contractions of regional muscles. According to this view, the development of any bone-weakening disease should be related to either (1) an intrinsic illness of the system (primary disturbances of bone cells), (2) a lack of mechanical stimulation (disuse-induced bone losses), or (3) a systemically-induced shift of the system's setpoint (systemic or secondary bone diseases). This short review aims to conciliate those views: (1) taking profit of the diagnostic possibilities provided by densitometric bone 'mass' determinations; (2) proposing other resources to assess bone mechanical properties; and (3) analyzing the muscle-bone interactions. These are crucial for achieving a differential diagnosis between disuse and primary or secondary bone disturbances, based either (1) on the densitometric determination of bone and muscle masses that would provide an anthropometric diagnosis of osteopenia (not osteoporosis because no extrapolations to bone strength can be made this way) or (2) on the cross-sectional analyses of bone structure or strength and muscle strength provided by bone tomography, magnetic resonance or other techniques that could afford a diagnosis of osteoporosis according to biomechanical criteria.

Aged↗

PubMed2003

[Toward an anthropometric diagnosis of osteopenia and a biochemical diagnosis of osteoporoses].

The current (metabolic) conception of bone-weakening diseases regards bone strength as determined by a systemically-controlled "mineralized mass" which grows until it reaches a peak and then is lost at individually-specific rates. This concept disregards bone biomechanics. Skeletons are structures, it reaches of which depends on the stiffness and the spatial distribution rather than the volume of the calcified material. Rather than allowing a systemic regulation of their "mass" as a way to optimize their strength, bones autocontrol their stiffness by orienting bone formation and destruction as locally determined by the directional sensing, by osteocytes, of the strains caused by mechanical usage (gravity, muscle contractions). Bone mass and strength are just side products of that control. Endocrine-metabolic systems modulate non-directionally the work of bone cells as required for achieving a mineral equilibrium, despite the biomechanical controls, and can determine osteopenias and osteoporoses. Osteoporoses are not "intense osteopenias" (as per the current WHO's conception) but "osteopenic bone fragilities" (as recently stated by the NIH). The diagnosis of osteopenia is an anthropometric problem that can be solved densitometrically; but that of bone fragility is a biomechanical matter that requires evaluation of bone material's stiffness and distribution by other means ("resistometry"). For therapeutic purposes, osteopenias and osteoporoses should be also evaluated according to the relationship between bone mass or strength and muscle mass or strength in order to distinguish between "mechanical" (disuse) and "metabolic" etiologies (intrinsic bone lesion, or systemic disequilibrium), in which the bone/muscle proportionality tends to remain normal or to deteriorate, respectively.

Anthropometry↗

PubMed2002

Emerging views about "osteoporosis", bone health, strength, fragility, and their determinants.

Recent articles by Drs. Lanyon, Raisz, Seeman, and Skerry summarized some emerging views about the causes and nature of some effects of mechanical loading on bones and "osteoporosis", the causes of fractures in that condition, and the causes of increased bone fragility and age-related bone loss. This article would supplement theirs with further evidence and ideas. This includes a definition of bone health that suggests currently popular classifications of "osteoporosis" and "osteopenia" could fail to distinguish healthy differences from normal averages from true bone diseases. This definition also suggests a classification of osteoporotic fractures that could question some current methods and uses of noninvasive absorptiometry. This article emphasizes concepts and generalities, and leaves resolution of any devils in the details to other places, times, and people.

Animals↗