Training Course in Reproductive Health/Chronic Disease
Osteoporosis in the frail elderly:
A special case?
and Jean-Philippe Bonjour, M.D.
Division of Bone
WHO Collaborating Center for the Prevention of Osteoporosis
Department of Internal Medicine
1211 Geneva 14
See also :
Among the determinants of osteoporosis in elderly,
nutritional deficiencies certainly play a significant role. Indeed,
undernutrition is often observed in elderly, and it appears to be more severe in
patients with hip fracture than in the general aging population. A variety of
evidences also leads to the conclusion that protein intake far below Recommended
Daily Allowance could be particularly detrimental for both the acquisition of
bone mass and the conservation of bone integrity with aging. Protein
undernutrition can favor the occurrence of hip fracture by increasing the
propensity to fall as a result of muscle weakness and of impairment in movement
coordination, by affecting protective mechanisms, such as reaction time, muscle
strength, and thus reducing the energy required to fracture an osteoporotic
proximal femur, and/or by decreasing bone mass. Furthermore, a reduction in the
protective layer of soft tissue padding decreases the force required to fracture
an osteoporotic hip.
II. Osteoporotic fracture
Various studies have found a relationship between the
level of protein intake and calcium-phosphate or bone metabolism and have come
to the conclusion that either a deficient or an excessive protein supply could
negatively affect the balance of calcium. An indirect argument in favor of a
deleterious effect of high protein intake on bone is that hip fracture appears
to be more frequent in countries with high protein intake of animal origin. But,
as expected, the countries with the highest incidence of hip fracture are those
with the longest life expectancy. In the large Nurse Health Study a trend for a
hip fracture incidence inversely related to protein intake has been reported.
Similarly, hip fracture was higher with low energy intake, low serum albumin
levels and low muscle strength in the NHANES I study. In a prospective study
carried out on more than 40'000 women in Iowa, higher protein intake was
associated with a reduced risk of hip fracture. The association was particularly
evident with protein of animal rather than vegetal origin. Similarly, a reduced
relative risk of hip fracture was found with higher intake of milk. In another
survey, no association between hip fracture and non-dairy animal protein intake
could be detected. However, fracture risk was increased when a high protein diet
was accompanied by a low calcium intake. Increasing protein intake has a
favorable effect on BMD in elderly receiving calcium and vitamin D supplements.
A low plasma albumin level has been repeatedly found in patients with hip
fracture as compared to age-matched healthy subjects or to patients with
III. Bone mass
Regarding the relation with bone mineral mass, there was
a positive correlation with spontaneous protein intake in premenopausal women,
bone mineral mass was directly proportional to serum albumin, taken as a
reflection of nutritional intakes, in hip fracture patients. In a survey carried
out in hospitalized elderly patients, low protein intake was associated with
reduced femoral neck areal bone mineral density (BMD) and poor physical
performances. The group with high protein intakes and a greater BMD,
particularly at the femoral neck level, had also a better improvement of
bicipital and quadricipital muscle strength and performance, as indicated by
the increased capacity to walk and climb stairs, after four weeks of
hospitalization. There was a positive correlation between radial bone mineral
content and protein intake in Japanese or American women. In a longitudinal
follow-up in the frame of the Framingham study, the rate of bone mineral
was inversely correlated to dietary protein intake. In contrast, in a
cross-sectional study, a protein intake close to 2 g/kg body weight was
associated with reduced bone mineral density only at one out of two forearm
sites in young college women. In the Study on Osteoporotic Fractures (SOF), an
inverse relationship between bone mineral density changes and the
animal-to-vegetal protein ratio was found. The higher this ratio, the greater
the bone loss. However, it would appear more relevant to compare with absolute
protein intakes than with a ratio. Taken altogether, these results indicate
a sufficient protein intake is mandatory for bone health. Thus, whereas a
gradual decline in calorie intake with age can been considered as an adequate
adjustment to the progressive reduction in energy expenditure, the parallel
reduction in protein intake may be detrimental for maintaining the integrity
function of several organs or systems, including skeletal muscles and bone.
IV. Relation with IGF-I
In association with the progressive age-dependent decrease
in both protein intake and bone mass, several reports have documented a
decrement in IGF-I plasma levels. Experimental and clinical studies suggest that
dietary proteins, by influencing both the production and action of growth
factors, particularly the Growth Hormone (GH)-Insulin-like Growth Factor (IGF)
system, could influence bone homeostasis. The hepatic production and plasma
level of IGF-I is under the influence of dietary proteins. Protein restriction
has been shown to reduce IGF-I plasma levels by inducing a resistance to the
action of GH at the hepatic level. Decreased serum IGF-I has been found in
states of undernutrition such as marasmus, anorexia nervosa, celiac disease or
HIV infected patients. Refeeding the patients led to an increase of IGF-I.
Furthermore, elevated protein intake is able to prevent the decrease in IGF-I
usually observed in hypocaloric states. In addition, protein restriction could
render target organs less sensitive to IGF-I. When IGF-I was given to rats
maintained under a low protein diet at doses normalizing its plasma levels, it
failed to restore skeletal longitudinal growth. In addition, Growth hormone
treatment was even associated with a decreased bone strength under conditions of
a low protein diet.
V. Protein replenishment and osteoporosis
A state of undernutrition on admission, which is
consistently documented in elderly patients with hip fracture, followed by an
inadequate food intake during hospital stay can adversely influence their
clinical outcome. Intervention studies using supplementary feeding by
nasogastric tube or parenteral nutrition, or even a simple oral dietary
preparation that normalizes protein intake can improve the clinical outcome
after hip fracture. This way of correcting the deficient food intake has obvious
practical and psychological advantages over nasogastric tube feeding or
parenteral nutrition. It should be emphasized that in our studies a 20 g protein
supplement brought the intake from low to a level still below RDA (0.8 g/kg
weight), avoiding thus the risk of an excess of dietary protein. Follow-up
showed a significant difference in the clinical course in the rehabilitation
hospitals, with the supplemented patients doing better. Although the mean
duration of dietary supplementation did not exceed 30 days, the significantly
lower rate of complication (bedsore, severe anemia, intercurrent lung or
infections, 44% vs 87%) and of deaths (40% vs 74%) was still observed at six
months. The duration of hospital stay of elderly patients with hip fracture
not only determined by the present medical condition, but also by domestic and
social factors. In this study, the total length of stay in the orthopedic
and rehabilitation hospitals was significantly shorter in supplemented patients
than in controls (median: 24 vs 40 days). It was then shown that normalization
of protein intake, independently of that of energy, calcium and vitamin D,
in fact responsible for this more favorable outcome. Finally, this normalization
of protein intake was found to increase IGF-I, and even IgM concentrations.
Thus, the lower incidence of medical complications observed after such a
supplement is also compatible with the hypothesis of IGF-I improving the immune
status, as this growth factor can stimulate the proliferation of immunocompetent
cells and modulate immunoglobulins secretion.
Beside the production and action of the growth hormone-IGF-I
system, protein undernutrition can be associated with alterations of cytokines
secretion, such as interferon gamma, tumor necrosis factor alpha (TNF-alpha), or
transforming growth factor beta. TNF-alpha and Interleukin-6 are generally
increasing with aging. In a situation of cachexia, such as in chronic heart
failure, an inverse correlation between bone mineral density and TNF-alpha
levels has been found, further implicating a possible role of uncontrolled
cytokines production in bone loss. Increased TNF-alpha can be a crucial factor
in the sex hormone deficiency-induced bone loss, but it also plays a role in the
target organ resistance to insulin, and possibly to IGF-I. Along the same line,
certain amino acids given to rats fed a low protein diet can increase the liver
protein synthesis response to TNF-alpha. The amino acid oxidation rate was lower
in children with kwashiorkor, who were repleted with milk rather than with egg
white, and protein breakdown and synthesis correlated inversely with TNF-alpha
levels. The modulation by nutritional intakes of cytokines production and
action, and the strong implication of various cytokines in the regulation of
bone remodeling suggest a possible role of certain cytokines in the
There is a large body of evidences linking nutritional
intakes, particularly protein undernutrition and replenishment, to bone
homeostasis and osteoporotic fractures. Several mechanisms, among them the
growth hormone-IGF-I-target organ axis and various cytokines, are likely to be
VI. Protein replenishment and other systems
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