Orthopaedic Surgery/Bone Mineralisation

Osteoporosis places 10 million Americans at risk for avoidable fracture and will only get worse given the demographics we face as the first of 78 million baby boomers hit 60 years of age this year. Osteoporosis is a challenge which is seemingly the cost of our success in achieving longevity and a life of relative ease. We drive cars, we work in offices, we buy our food, we spend our leisure in sedentary ways, and we survive to old age, spared from random violence, accident, and starvation. These benefits of modern life have occurred in such a short time frame, our physical being has certainly evolved to a different set of demands. Lacking the physical demands upon our skeleton it suffers disuse with resultant loss of functional reserve rendering us vulnerable in later years to fracture either with the event of a slip and fall, or from unexpected sudden loads, and in the worst case with just the usual mechanical stresses of daily use.

Osteoporosis is a side effect of modern life and the leisure and longevity it bestows. An active effort to offset this side effect should be accepted, but it seems that even simple measures such as dietary supplementation lack efficacy by virtue of poor compliance over time, even though such measures are inexpensive and seemingly benign in their demands on our time and lacking onerous side effects. How then can we expect to have a meaningful impact on the incidence of osteoporosis related fractures with a prescription of regular exercise and strength training? Education has an important but ultimately limited role in affecting culture and behavior, but education is our main tool and is most effective when repeated at regular intervals and in varied iterations, the desired message slipped under the door and sprung like a product placement spot in the midst of a favorite movie, or dangled from the wrist of a favorite celebrity.

Given the complex events giving rise to the prevalence of osteoporosis it is not surprising that dietary supplementation alone would have only a modest demonstrable effect in preventing the problem. A variety of environmental metabolic and behavioral factors interact with the predominant genetic factors to contribute to osteoporosis. The disease spectrum includes those in whom Vitamin D and Ca are the predominant factors and those in whom the depletion of hormonal regulation of the normal bone remodeling cycle is lost.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16481635

http://archinte.ama-assn.org/cgi/content/abstract/166/8/869?maxtoshow=&HITS=&hits=&RESULTFORMAT=&fulltext=calcium+and+fractures&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

Post menopausal osteoporosis is the typical example of the latter in that the compressive strength of bone is lost at an average 8.5% per decade from age 20 till age 100. Bone mineral density (BMD) declines in an accelerated manner after menopause at approximately 2% per year and this mineral density is responsible for 92% of the compressive strength. The loss of strength is somewhat mitigated by the increase in bone diameter and thus a theoretically enhanced bending stiffness. Male testosterone and Estrogen levels decline as well but there is a larger baseline bone mass and therefore a lesser tendency toward fragility fracture in males.

The effect of the sex hormones is to regulate the bone remodeling cycle. In the absence of sex hormones the bone remodeling cycle is accelerated with the net effect of bone loss. The osteoblastic phase takes longer than the osteoclastic phase so when the cycle speeds up the net effect favors osteoclasis. Imagine if we changed the rules of a hockey game by increasing the number of periods and shortening the length of the breaks in which the Zamboni must restore the surface. As the breaks shorten they cannot complete the task and with the shorter periods of play the well rested players tear up the ice with greater efficiency.

Skin pigmentation protects against the harmful effects of solar UV exposure which can cause skin cancer. UV B is necessary for endogenous production of Vitamin D in the skin, and most humans require sun exposure to satisfy their need for Vitamin D. Where sunlight is abundant, darker skin still allows sufficient UV absorption for Vit D synthesis but in northern climates lighter skin is needed to allow for sufficient UV absorption except in coastal areas where dietary Vitamin D makes skin synthesis a lesser priority and thus darker skin pigmentation is also seen. Skin pigmentation varies to calibrate sufficient UV absorption and to mitigate the harmful effects of excessive exposure. Darker skin pigmentation in combination with limited sunlight exposure and deficiency in dietary calcium adds to the risk of Vit D deficiency rickets and to osteoporosis and osteomalacia in adults.

Vitamin D is made in the skin by solar ultraviolet B radiation absorption by 7 dehydroxycholesterol to form a precursor molecule of Vitamin D3 which converts rapidly to Vitamin D3. Vitamin D3 is converted in the liver to 25-hydroxyvitamin D3 and then in the kidney to the active form 1,25-dihydroxyvitamin D3. Vitamin D in the form of 1,25-dihydroxyvitamin D serves to facilitate the bioavailability of circulating calcium for the skeleton, and facilitates deity calcium absorption. The skeleton too serves as the back up reservoir to maintain serum calcium levels within physiologic levels for optimum neuro-muscular function. When dietary sources of Calcium and Vit D are lacking secondary hyperparathyroidism can lead to osteoporosis.

Dietary supplementation of both calcium and Vitamin D becomes increasingly important after age 50. Recommended supplementation of 1200 mg of calcium and 400 IU of Vit D in women over age 50 is designed to achieve a serum 25-OH Vit D level of 20 ng/ml. 5 to 10 minutes exposure of the arms and legs to sunlight, 2-3 times per week, is another method to maintain Vit D in a fashion which combines nicely with regular exercise.

http://www.loc.gov/catdir/description/random0413/2003066679.html

http://www.ajcn.org/cgi/content/full/80/6/1678S?maxtoshow=&HITS=&hits=&RESULTFORMAT=1&andorexacttitle=and&fulltext=Vitamin+D++and+sunlight&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT

Collagen is the major structural protein of vertebrate extracellular matrix. Procollagen is processed to collagen which then associates into fibrils. Bone is a calcified organic matrix with a micro-composit structure of collagen and hydroxyapatite, Ca5(PO4)3OH. The structural qualities responsible for the apparent toughness of bone remain unclear. The atomic force microscope is being used to study the nature of bonding especially the cross linking within fibrillar collagen. The working hypothesis supported by preliminary experiment suggests sacrificial bonds which rupture and readily reform in response to strains. The modulation of mineralization leads to a balance between material properties of stiffness and brittleness. The unique structure of bone allows for an unusual toughness in addition to its stiffness.

http://www.biophysj.org/cgi/content/abstract/89/1/536?maxtoshow=&HITS=&hits=&RESULTFORMAT=1&andorexacttitle=and&fulltext=atomic+force+microscope+and+collagen&andorexactfulltext=and&searchid=1&FIRSTINDEX=20&sortspec=relevance&resourcetype=HWCIT http://www.nature.com/nature/journal/v399/n6738/abs/399761a0_fs.html;jsessionid=1BF7DE6C4A8FEDC2C8BA70DD035E288E