IMPLANTOLOGY: RISK FACTORS FOR OSTEOPOROSIS AND OTHER METABOLIC BONE DISEASES BONE PHYSIOLOGY AND METABOLISM IN DENTAL W. Eugene Roberts DDS, PhD" Kirt E, Simmons DDS, PhO"* Lawrence P. Garett PhD” Rolando A. DeCastro DMD, MSOt Placing a dental implant elicits a time-dependent bone response controlled by wound healing factors (cytokines, bioelectrical signals), biomechanics (gravitational, func- tional, and therapeutic loads), and mineral metabolism (harmones, diet, excretion) The osseous response to an implant involves four physiological stages: (1) endosteal and periosteal callus formation; (2) compaction and remodeling of the callus; (3) remodeling (turnover) of the nonvital interface and adjacent bone; and (4) maturation (secondary mineralization) of new bone. Long-term maintenance of a rigid implant interface is related to continual bone remodeling. Common metabolic bone disorders affecting potential implant patients are osteopenia (“osteoporosis"), renal osteodystro- hy, osteomalacia, and Paget's disease. The most prevalent problem is a long-term negative calcium balance leading to a compromise in bone strength. Symptomatic osteoporosis (usually wrist, hip, and/or spine fractures) affects 4 to 50 percent of the population depending on age, race, sex, endocrine status, and life-style. Postmenopau- sal white and Asian females present the greatest risk. The jaws of “osteoporotic” ‘adults are variably affected because of the moderating influence of mechanical function. ‘Management of metabolic bone disorders is an important consideration in diagnosis, treatment planning, and long-term monitoring of dental implants. Bone metabolic ‘counseling, a natural extension of preventative dentistry, is an unexpected benefit readily appreciated by patients and their families. (Implant Dent 1992;1:11-21) jonsistent clinical success with dental implants'~* requires careful attention to fundamental physio- logical principles.‘ Host response to an endosseous de is determined by (1) appropriate patient selec- tion; (2) precise, atraumatic surgical procedures;** (3) biocompatibility;*® and (4) biomechanical fac- tors.***” Wakley and Baylink™ introduced the concept of metabolic bone disease to the dental implant field. Recently, Roberts et al’* published a brief, clinically oriented review of the risk factors for osteoporosis. Osteoporosis is a generic term for low bone mass (osteopenia). Depending on life-style, the incidence of osteoporosis (signs and/or symptoms of osteopenia) is race, age, and sex dependent. Older white and Asian + Proessr and Chaban, Department of Otters, ‘Assetan Prtessr, Doparnent of Orta, “Aesant Projessor an Orecter, Bore Research Labor. + Professor and Drectr Dnt! At Indana Unversty Schoo of Deny Indanapets, 46202 1s3n 1os6.616/2/0101.01183.070 Wotan Numer Copyright ©1982 by Wom & Wikins ‘women are the highest risk group; up to 50 percent have signs and/or symptoms of inadequate bone strength." However, osteoporosis is a pervasive disease that can affect essentially all elements of society; even low risk groups (black, male, ete.) may have an incidence of 4 to 6 percent." Osteoporosis is an immense health prob- Jem resulting in 1.2 million fractures per year at a total health care cost of $7 to 10 billion."* A carefal history is the best screening method to determine which dental patients should be referred for a thorough medical ‘work-up prior to extensive surgical and restorative pro- cedures. Diagnosis of osteoporosis is usually established by bone mineral density measurements (photon absorp- tion) of the radius, spine, hip, and/or heel."* Treatment depends on a careful assessment of etiology. The objectives of this article are to present a succinct, clinically oriented discussion of (1) metabolic influences on the osseous reaction to dental implants; (2) funda- mental aspects of bone metabolism; (3) specific ques- tions for risk evaluation of a potential implant patient; and (4) guidelines for referring high risk patients to an appropriate physician for evaluation. Within the med- ical sciences, dentistry has an enviable reputation for disease prevention. Screening for metabolic bone dis- orders is a natural extension of dental practice that is readily appreciated by patients.12 Fig. 1. Three-dimensional atst’s rendition of a 4-month heal- ing petiod in human cortical bone. Osteoclasts are resorbing the periosteal callus. Remodeling (tumover) of the nonvital Interface and adjacent cortical bone is mediated by cuting/ filing cones of osteoclasts and osteoblasts. BONE RESPONSE TO DENTAL IMPLANTS When implants are placed in cortical bone, the initial healing reaction is a woven bone callus at the periosteal and endosteal surfaces. Production of an external callus is limited by traumatic surgery, particularly extensive periosteal stripping. A substantial portion of the callus, is converted to lamellar bone by compaction and re- modeling to provide rigid stabilization of the implant within bone. From about 6 to 18 weeks, there is intense remodeling of the interface and adjacent supporting bone. Implants placed in good quality bone are usually loaded during the late remodeling phase (3 to 6 months). Figure 1 shows a cylindrical dental implant with a calcium phosphate coating in the advanced remodeling stage, ie, a about the time to uncover the implant (3 to, 4 months). Figure 2 demonstrates similar remodeling of the interface and supporting bone adjacent to a threaded titanium (Brinemark) implant. Initial func: BONE PHYSIOLOGY AND METABOLISM Fig. 2. Multiple bone la- bets (colored ines) dem- onstrate intense remod= ‘ling atthe interface and within adjacent bone supporting a Branemark. implant in adult dog mandible. There was an unloaded healing phase of 8 weeks followed by 20-week loaded period. The bone labels were administered at 2-week intervals. tional loading should be moderate because full matu- ration of the newly formed bone is not complete for up to 1 year Bridges connecting implant-supported abutments should be rigid to avoid localized osseous, overloads due to prosthesis flexure.IMPLANT DENTISTRY + SPRING 1992 Histological details of bone healing and maturation are published,'*” but there is litle information on the biomechanical and metabolic factors involved. The o3- seous response to a dental implant is controlled by a time-dependent interaction of wound-healing (cyto- kines, bioelectrical signals, etc.), biomechanical (gravi- tational, functional, and therapeutic loads), and meta- bolic (hormones, diet, excretion) factors. In general, metabolism has its strongest influence on bone resorp- tion while bone formation is primarily controlled by mechanical factors.** !? This report focuses on the met- bolic aspects of dental implantology. The complexity of the control mechanisms leaves many opportunities for the aberration of normal physiology by a variety of disease processes. PHYSIOLOGICAL MECHANISMS OF BONE METABOLISM Bone is the primary calcium reservoir of the body. Approximately 99 percent of the caleium in the body is stored in the skeleton. Constant remodeling (internal turnover) mobilizes and redeposits calcium by coupled resorption and formation events (Figs. 1 and 2). This continual flux of bone mineral responds to a complex hierarchy of endocrine, biomechanical, and cell level control factors to maintain the serum calcium level at about 10 mg/dl (10 mg percent). In effect, the body maintains the primordial environment in which cellular processes evolved (Fig. 3). Evolutionary theory holds that life first evolved in the sea, a calcium-rich broth. For this reason, marine animals rarely experience problems with calcium me- tabolism. As evolving species moved onto land, it was, physiologically essential to develop elaborate means for storing and conserving caleium. For instance, snails 13 store and recover calcium from their shells while mam- mals utilize the skeleton for the same purpose. Even moderate decreases in serum calcium levels are incom- patible with life, so bone metabolic mechanisms are primitive, highly conserved processes that have a pro- found influence on all aspects of bone physiology. Calcium homeostasis is the process by which mineral equilibrium is maintained. Bone mass is sacrificed when substantial amounts of calcium are needed to maintain serum levels. Under conditions of negative calcium balance, the body will resorb osseous supporting struc- tures to the point of spontaneous failure. Basilar bone of the jaws, as well as the alveolar processes, is subject to metabolically driven bone atrophy.’ “7 ‘The kidney is the primary calcium conservation or- gan in the body. Through a complex series of exeretive and endocrine functions, excess phosphate is eliminated while calcium is conserved (Fig. 4). Patients with im- paired renal function are usually high risks for osseous surgical procedures. Kidney disease is often manifest as secondary hyperparathyroidism with impaired vita- min D metabolism. Renal osteodystrophy results in poor bone quality because of fibrous dysplasia and an inhibition of mineralization (Fig. 5)."* Patients with Jess than 80 percent normal kidney function (creatinine clearance, etc.) are often poor risks for dental implant, procedures because they usually present some signs of renal osteodystrophy (high turnover, fibrous dysplasia, and excessive unmineralized osteoid).”” Absorption from the small intestine is the primary exogenous source of calcium and phosphate. Phosphate is passively absorbed and rarely deficient, while optimal calcium uptake requires an active absorption mecha- nism, A unique factor involved in the gut absorption process is calcium-binding protein, formed in response to the active metabolite of vitamin D (Fig. 4). Com- mon clinical profiles associated with poor ealeium ab- ¥ THO = Fig. 3. A schematic drawing of the principal pathways for, calcium metabolism. Under conditions of zero calcium balance, ‘the 300 mg of calcium lost dally through gut secretion (200 mg) land kidney excretion (100 mg) must be offset by 300 mg of ‘absorption from the diet. Adapted from Wakley and Baylink.*® trot Eben | | Or eaoraie co Reserton Lorem snes Fig. 4. Calcium conservation involves a cascade of regulatory ‘events inthe blood, parathyroid glands, kidney, gastrointestinal ‘tract (gut), and bone. There are immediate, short-term and long-term effects on calcium mobilization trom bone. Sustained ‘demand for calcium due to dietary insufficiency or metabolic disease requires resorption of bone which may compromise skeletal strength4 BONE PHYSIOLOGY AND METABOLISM Fig. 5. Renal osteodystrophy, as evidenced by fbrous dysplasia and excessive osteoid (purple), is noted in an undemineraized section of trabecular bone from the iliac crest of a patient with chronic Kidney insufficiency. This Masson-stained specmen was provided by Dr. Flemming Melsen, Arhus, Denmark (orignal magnification x60). Fig. 6. Ostoomalacia, a evidenced by excessive unmineralzed osteod (purple). noted n an underineraized section of trabecular bone from the lise crest of a patient with vitamin D deficiency. This Masson-stained specimen was provided by Dr. Flemming Melsen, Arhus, Denmark (original magnification x60). Fig. 10. Utravolt microscopy ofa 100-um section demonstrates double bone labels near the interface ofan implant used for 4 years a a source of orthodontic anchorage. The high rate of labeling indicates @ bone remodeling rate of about 30 percent per year. In adction to its essential metaboic roe, the bone remodeling process apparently helps maintain “osseointegration” via step- wise replacement of fatigued bone at the interface * Fig. 11. Multiple fuoroshrome labeling (2-week intervals) demonstrates the metaboc and structural fractions of young adut rabbit Cortical bone. Bone strength rig) isereatly increased by adcing thin layers of new bone atthe periosteal surface (ft) Rapicly remodeling secondary osteons (lt) are a ready avaiable source of metaboic caleum. Loss of the metabolic fracton nr portion (ofthe cortex) has relatively iti fect on bone strengthIMPLANT DENTISTAY + SPRING 1982 sorption are aging, estrogen deficiency, gastrointestinal problems, vitamin D deficiency, and kidney disease. Vitamin D deficiency often results in osteomalacia (Fig. 6). Because of poor healing potential and inadequate strength, osteomalacic bone is unsuitable for dental implant procedures. Diagnosis of osteomalacia presents special problems because it can only be confirmed by a biopsy. CALCIUM HOMEOSTASIS Osteopenia (low bone mass), the most common bone metabolic disorder, is usually an aberration of the cal- cium homeostatic mechanism. To effectively deal with these problems, clinicians need at least a working knowledge of this relatively complex process. Figure 4 is a flow chart of the major organ systems involved. ‘The skeleton provides calcium to support metabolic needs by three temporally related mechanisms: (1) an immediate (within seconds) flux of calcium from bone fluid; (2) a short-term response (minutes-days) of os- teoclasts and osteoblasts; and (3) long-term control (weeks-months) of bone turnover (Fig. 4). Precise reg- ulation of serum calcium levels is essential for nerve ‘and muscle conductivity. Low serum calcium can result, in tetany and death. Sustained high serum calcium, a ‘manifestation of hyperparathyroidism and some malig- nancies, is also detrimental. It may lead to kidney stones and dystrophic calcification of soft tissue." Instantaneous regulation of calcium homeostasis is ‘accomplished in seconds by selective transfer of calcium ions into and out of bone fluid (Fig. 7). Bone fluid is separated from extracellular fluid by osteoblasts or the relatively thin “bone lining cells” thought to be derived from osteoblasts. A decreased serum calcium level stim- ulates secretion of parathyroid hormone (PTH). PTH. ‘enhances transport of calcium ions from bone fluid into ‘osteocytes and bone lining cells. The active metabolite of vitamin D (1,25-dihydroxycholecaleiferol, abbrevi- ated 1,25-DHCC) enhances pumping of calcium ions from bone lining cells into extracellular fluid. This sequence of events transports calcium across the bone lining cell, resulting in a net flux of calcium ions from bone fluid to extracellular fluid.” To a limited extent, it is possible to support calcium homeostasis without resorbing bone. Radioisotope studies confirm that there isa diffuse mineral component within bone that can be mobilized or redeposited without bone resorption or formation.”* However, sustained negative caleium bal- ance can only be compensated by resorbing bone. Short-term control of serum calcium levels affects rates of bone resorption and formation within minutes 6 Fig. 7. An endocrine-mediated shit (PTH, 1,25-DHCO) in bone {luid equilorium can raise serum calcium in Seconds by trans- {ering calcium from bone fluid, across bone lining cells and ‘osteoblasts, to extracellular fuid. Calcitonin (CT) inhibits cal cium transfer to ECF. Bone resorption by osteoclasts is en- hhanced by PTH and inhibited by CT. via the three calcific hormones: PTH, 1,25-DHCC and calcitonin (CT). In concert with PTH, i,25-DHCC (1) enhances osteoclast recruitment from’ promonocyte precursors;"* (2) increases the resorption rate of existing osteoclasts" and (3) may suppress the rate of bone formation by existing osteoblasts. Both hypermineral- ized and hypomineralized bone growth arrest lines have been described. The former are features of normal differential growth and the latter reflect physiological disturbances such as birth (neonatal line) or space Aight. CT is produced by parafollicular C cells in the thyroid gland, It decreases serum calcium by transiently sup- pressing osteoclastic resorption. Despite the continual presence of CT, the inhibitory effect on osteoclasts is Jost after about 24 to 48 hours (“escape phenome non”).** Since elevated serum calcium is rarely @ problem under normal conditions, the physiological role Of CT in calcium homeostasis of humans is unclear. It may be vestigial or have a presently unknown extra- skeletal function. However, CT is of considerable phar ‘macological significance because it is used to treat osteoporosis. Cyclic use of CT avoids the osteoclastic escape phenomenon and helps preserve the skeleton by inhibiting resorption. CT also has bone analgesic prop: erties.*""" The disadvantages of CT are its relative expense and the fact that it cannot be taken orally. It is usually administered by nasal spray. Fig. 12. Continual remodeling of trabecular bone in the mandibular condyle of a young adult rabbit labeled at 1-wweek intervals is noted in a 15-um section at 100. Fig. 13. High rate of remodeling is demonstrated by multiple fluorochrome labeling in trabecular bone supporting a rigid titanium Implant in an aduit sheep (original magnification x 100).16 Long-term effects of metabolic status on the skeleton are profound. Biomechanical factors (normal function, exercise, posture, habits, etc.), other hormones (sex steroids, growth hormone, etc.), and the metabolic mechanisms previously discussed (Figs. 3 and 4) dictate ‘mass, geometric distribution, and mean age of bone.”* Mass and geometric distribution of bone are strongly influenced by load history (biomechanics) and sex hor- mone status. PTH is the primary regulator of remod- cling frequency, ie, coupled turnover events within bone (Fig. 8). Since the adult skeleton is composed almost entirely of secondary (remodeled) bone, the PTH-me- diated activation frequency determines mean bone age. Bone age is an important determinant of fragility be- cause old bone is usually more weakened by fatigue damage (Fig. 9). A clinical correlation to dental im- plants is the high bone remodeling rate noted at the interface of a titanium implant loaded for over 3 years in an adult man (Fig. 10). Continual remodeling of the ‘bone interface may be crucial to maintaining rigid fixation (“osseointegration”). Both trabecular and cortical bone turn over through- ut life by two fundamentally distinct mechanisms: (1) modeling—independent sites of resorption and forma- tion that change the form (shape and/or size) of a bone and (2) remodeling—coupled sites of resorption and formation that replace previously existing bone (Fig. 8). Modeling is largely under mechanical control, ie, sites of bone modeling (M) and remodeling (R). Via the drift Phenomenon, modeling bones can change their shape or po- sition. Remodeling is turover of existing bone. (From the Journal of the indiana Dental Association with permission.) BONE PHYSIOLOGY AND METABOLISM CC > Rs -ES OF Fig. 9. Fragle bone can be fractured by minimal trauma (1n- jury). Factors contributing to fragility are low bone mass, con- nections between trabecular bone (connectivity), and accumu lation of fatigue damage. Increase in mean bone age is the ‘major factor in accumulation of fatigue damage. bone strain or flexure which generates streaming poten- tials and cell level prostaglandin synthesis." On the other hand, remodeling responds primarily to metabolic mediators (PTH, probably in concert with 1,25-DHCC). Despite clear physiological distinctions, bone modeling and remodeling are interrelated. For instance, internal remodeling (Fig. 8) compromises the rigidity of a bone which may in turn trigger compensatory modeling at. the bone surface.‘ Continual turnover of bone through- out life provides a short-term mechanism for control- ling serum calcium by regulating the rates of bone resorption and formation. ‘A good morphological distinction for understanding the interrelationship of bone modeling and remodeling is the concept of structural and metabolic fractions (Fig. 11). For cortical bone, the former is the outer half ofthe diaphysis and the latter is the inner half. Stiffness and strength of a bone is rapidly enhanced by adding circumferential lamellae at the periosteal surface. Even a thin layer of new osseous tissue greatly enhances bone rigidity because it increases the shaft diameter.”" On the other hand, new bone added at the endosteal surface has little effect on strength. Structurally, long bones and the mandible are modified osseous tubes, an opti- mal design for achieving maximum strength with min: imum mass.” Within limits, loss of bone at the endos- teal surface or within the inner third of the compact bone has little effect on bone strength. The inner cortex is rapidly remodeled and can be mobilized to meet metabolic needs without severely compromising bone strength. The structural fraction of cortical bone re- models relatively slowly (<10 percent per year). ‘Trabecular bone is the major source of metabolic calcium because of its high surface to volume ratio and elevated remodeling rate (20 to 30 percent per year). In effect, all trabecular bone is part of the metabolicIMPLANT DENTISTRY «SPRING 1992 fraction of the skeleton (Figs. 12 and 13). For this reason, bones like the maxilla are susceptible to rapid and severe atrophy under conditions of disuse and/or metabolic demand for calcium. Loss of structural sup- port by trabecular bone is responsible for most of the spontaneous fractures associated with osteoporosis. ‘The concept of structural and metabolic fractions has considerable clinical significance: (1) high dietary cal- cium (21200 mg/d) is essential during adolescent. growth (Table 1) to provide structural strength without compromising the metabolic reserve and (2) sustained negative calcium balance during adulthood thins the cortices from the inside out. Since the outer dimension of a bone is maintained, the low bone mass and overall poor quality of an atrophied implantation site is often not appreciated until the clinician attempts to place an implant. CALCIUM BALANCE Positive calcium balance during the growing years, and for about 10 years thereafter, results in a peak skeletal mass at about 25 to 35 years of age.® After the early adult years, natural aging is associated with a slightly negative calcium balance that progressively erodes bone volume throughout life. Zero caleium bal- ance is the ideal metabolic state for maintaining skel- etal mass." Preservation of bone requires a favorable diet, endocrine balance, and adequate exercise. Diet ‘The current recommended daily allowance of cal- cium, for adults over 19 years of age, is 800 mg of calcium/d. Growing adolescents, pregnant or lactating ‘women, and particularly pregnant teenagers need even, more (Table 1). Because of calcium abundance and bioavailability, dairy products are a major dietary source of calcium. About 75 percent of the available calcium in the North American food chain is in milk products. A diet excluding dairy products usually re- quires calcium supplementation. Dietary Calcium Recommendations Calum Group Age (mq) infants mo 360" 6-12 mo 540" Children 1t0y 800" Adolescents 11-18 y 1200° ‘Young aduits 19yandover 800° Pregnant or lactating women Under 19 1600" Over19y 1200" Postmenopausal women with- 1500 ‘ut estrogen replacement” “Teme ay aoc ita NOuSDy ea Mra Day moan 7 It was previously thought the bone of postmenopausal women not receiving estrogen could be maintained with a high calcium diet (1500 mg/d). More recent studies show that dietary calcium is not effective during the first 5 to 7 years after menopause.™ It is now widely recommended that postmenopausal women receive es- trogen replacement therapy. Obesity has few health benefits, but it is a protective factor against osteoporosis," probably due to the high rates of mechanical loading required to move an over- ‘weight body. On the other hand, slight stature is a risk factor for osteoporosis. Because weight control is a concern for the population at risk, the calcium to ealorie ratio is an important consideration in dietary counsel- ing. As shown in Table 2, the most favorable dairy products with respect to the calcium to calorie ratio are nonfat milk, part-skim mozzarella cheese, Swiss cheese, and plain low-fat yogurt. Some adults avoid milk prod. ucts because of lactose intolerance. Lactose intolerance is usually manifest by an upset stomach or other gas- trointestinal symptoms. Even patients intolerant. of milk can usually consume cultured products like cheese and yogurt. Calcium supplements are indicated if a patient is allergic to milk or fails to achieve a calcium sufficient diet for any other reason, Other foods (meat, eggs, spinach, etc.) contain some calcium, but it is very difficult to consume adequate calcium in’a diet exchud- ing dairy products." Calcium supplements of many varieties are available in pharmacies and health food stores. Most will provide adequate calcium when used as directed. However, be- ‘ware of “bone meal” or “dolomite” because they often contain lead or other toxic metals. Among the least. Table 2. Calcium and Calorie Content of Common Dairy Product Calum (mg) Calories Ratio Mik ‘Whole, 9.9% fat, 1 cup 201 180 1.8:1 Low-lat, 2% fat, 1 cup 297 120 251 Buttermilk, 1 cup 285 1002.81 Skim milk, 0% fat, 1 cup 30285 Cheese ‘American, pasteurized process, 174 104 1.7:1 1oz ‘Choddar, 1 02 204115 1.81 Cottage, creamed, 4% fat, 1 cup 135 285 O.6:1 Cottage, low fat, 2%, 1 cup 155 205 08:1 Monterey Jack, 1.02 212 106 Mozzarella, part-skim, 1oz 20780 ‘Swiss, 1 oz 272 105 Yogurt Fruit, low fat, 8 02 345 23015: Pain, low fat, 8 oz 415 145 29: Plain, nonfat, 8 oz 45212536 ‘Ta rote saan aioe 0 nc ORNNST NEST Oa Se HOG yom mre ney hasan18 ‘expensive, readily tolerated supplements are calcium carbonate’ antacids (Tums, “Ca-rich” Rolaids, ete.) ‘When determining the elemental calcium in a supple- ment, remember to use the molecular weight. Since calcium carbonate is 40 percent calcium by molecular weight, a 500-mg tablet provides only 200 mg of ele mental calcium." Endocrinology Peptide hormones (PTH, growth hormone, insulin, CT, ete.) bind receptors at the cell surface and may be internalized with the receptor complex. Steroid hor- mones (vitamin D, androgens, estrogens, etc.) are lipid soluble and pass through the plasma membrane to bind receptors in the cytosol.” Excessive vitamin D is highly toxic as a result of its ready access to cells. Regular exposure to sunlight (a minimum of 10 percent of the skin for at least 30 min/d) is a better clinical strategy than vitamin D supplementation because overtreat- ment can be toxic. PTH increases serum calcium by both direct and indirect vitamin D-mediated effects. Although vitamin D was originally thought to be an essential dietary factor, it is not_a vitamin at all but a hormone.” Cholecaleiferol (“vitamin D”) is synthesized in skin irradiated by UV light, then hydroxylated in the liver at the #25 position and in the kidney at the #1 position to produce the active metabolite 1,25-DHCC (Fig. 8). Clinically, a major effect of 1,25-DHCC is induction of active calcium absorption from the gut. Because of the complexity of the vitamin D synthetic and metabolic pathways, calcium absorption may be inhibited at many. levels: (1) lack of skin exposure to adequate sunlight of the proper wavelength; (2) failure to compensate for a lack of vitamin D synthesis by consuming vitamin D in the diet; (3) a genetic defect in skin, liver, or kidney; (4) liver disease,” and/or (6) kidney disease.” ‘Sex hormones have profound effects on bone. Andro- gens build and maintain musculoskeletal mass. Estro- gen conserves skeletal calcium by suppressing the ac- tivation frequency of bone remodeling.” At menopause, remodeling activation events increase bone tumover. In the presence of negative calcium balance, there is a rapid loss of bone resulting in osteoporosis. Even young women are susceptible to significant bone loss if the menstrual cycle (menses) ceases. This is a common problem in women with low body fat that exercise intensely (running, gymnastics, etc.) or are anorexic. It is clear estrogen protects the female skeleton from bone loss during the child-bearing years.” Lack of menses (amenorrhea) in women with an intact reproductive system is a marker for estrogen deprivation. Paramenopausal women with partial hys- terectomies (retained ovaries) present a special problem because amenorrhea fails to serve as a physiological marker for estrogen depletion, Estrogen levels should bbe regularly monitored in these women so replacement. therapy can be promptly initiated when adequate levels BONE PHYSIOLOGY AND METABOLISM of estrogen are no longer maintained. It is important to initiate estrogen replacement therapy during the early stages of menopause because the highest rates of bone loss are immediately postmenopausal." Mechanical Loading Regular exercise helps build and maintain skeletal mass by muscular loading. Peak loads exceeding the minimal effective strain, 0.25 percent deformation or 2500 microstrain,“' induce anabolic bone modeling, ie, bone formation at the periosteal surface.* Streaming potentials (not “piezoelectric” signals) are generated within loaded bone and displaced periodontium. Loaded bones and teeth generate a unique separation of charge which is associated with a specific osteogenic response." Gravity Osteoblast differentiation leading to new bone for- mation is stimulated by mechanical loading" and in- hibited by weightlessness. Space flight studies have established that gravity helps maintain skeletal mass by supporting osteoblast production. A substantial por- tion of the physiological loading of the mandible is associated with antigravity posturing. In erect posture, gravity tends to open the mouth. Muscle force is used to hold the mandible in rest position. Apparently, due to a lack of postural loading, growth of the mandibular condyle is inhibited in space." From a clinical perspec- tive, loading of endosseous implants and supporting bone is a summation of muscular and gravitational forces associated with mastication, speech, antigravity posturing, and the direct effect of gravity on prostheses. CLINICAL CONSIDERATIONS Common age-related changes associated with patho- genesis of osteoporosis are (1) impaired vitamin D synthesis or metabolism; (2) inhibition of calcium ab- sorption; (3) increased PTH levels; (4) decreased CT levels; and (5) increased bone turnover (high remodel- ing frequency)."*? Drugs are also a major factor in the etiology of bone deficiencies. A number of phar- macologically active compounds have been implicated in bone loss: glucocorticoids, anticonvulsants, metho- trexate, cyclosporin, lithium, tetracycline, aluminum base antacids, nicotine, and heparin.” In addition to aging and a variety of drugs, the relative risk factors for osteopenia are slight stature, ow calcium diet, menopause or dysmenorrhea, low physical activity,’ smoking, alcohol, vitamin D’defi- ieney (often lack of exposure to UV light), kidney failure, liver disease (cirrhosis), and history of fracture associated with little or no trauma.”"*" Most charac- teristic of osteoporosis are fractures of the hip, distalIMPLANT DENTISTRY SPRING 1992 radius (Colles’ fracture), and vertebral body (crush frac ture). Multiple crush fractures of the spine contribute to stooped posture (dowager’s hump) and a loss of height. ‘Most medical questionnaires used in dental practice fail to address all of these important bone risk factors. Figure 14 is a list of pertinent questions for assessing bone health. The first two questions address. Paget’s disease, a malignancy of osteoclasts resulting in poor bbone quality. The other questions relate to osteopenia, osteomalacia (vitamin D deficiency resulting in poor mineralization), and renal osteodystrophy. Other met abolic problems like hyperparathyroidism are best. de- tected by blood chemistry, ie, elevated serum calcium and PTH levels. Ifa careful history suggests the prob- ability of a metabolic bone disorder, the patient should be referred to an appropriate physician (specifically trained in bone metabolism) for evaluation prior to placing dental implants. Surveys show not all physi- cians are abreast of the complex field of bone metabo- lism. In choosing a physician for referral, it is impor- tant to be aware of his or her training. Otherwise, it is generally best to refer to a metabolic bone unit at major medical center. ‘THERAPEUTIC CONSIDERATIONS Clinical management of metabolic bone disease is one of the most rapidly advancing fields in medical science. Preventative measures, such as postmenopau- sal estrogen replacement therapy, are routine medical practice. However, established problems like sympto- atic osteoporosis, osteomalacia, renal osteodystrophy, and Paget’s disease are best managed in major medical centers by specifically trained physicians with direct access to sophisticated monitoring equipment. ous? ‘ee Peo Fig. 14. Medical history addendum—bone metabolism 19 Estrogen remains the leading preventative measure for postmenopausal osteoporosis. Furthermore, it is now considered an effective treatment for established osteoporosis.” Bisphosphonates” (etidronate for in- stance) also appear promising as a preventative meas- ure, Of the three most common therapeutic agents for ‘osteoporosis (calcitonin, bisphosphonates, and estro- gen), estrogen is preferable for a dental implant patient. Both calcitonin and bisphosphonates directly inhibit bone resorption, an important element of the bone healing and maturation process. On the other hand, estrogen acts by suppressing the metabolically driven, bone-remodeling frequency. Thus, it does not interfere with bone healing and the osseous response to mechan- ical loading. ‘There has been considerable interest in treating os- teoporosis by enhancing bone formation. Of the bone anabolic agents under consideration, fluoride was the ‘most promising because it increased bone mineral den- sity. Unfortunately, fluoritie bone is poorly organized and has little strength. It is not helpful in preventing the progressive fractures of osteoporosis. Therefore, fluoride is not recommended for treating osteoporosis. Other potential anabolic agents like PTH, growth hor- mone, and flurbiprofen are being tested in animals. At, present there is no reliable method for enhancing bone formation to treat osteopenia PRACTICE MANAGEMENT Metabolically compromised adults, presenting for dental treatment to correct unrelated restorative prob- lems, are often unaware of the risk. An astute dentist, can provide a profound health service by identifying individuals likely to benefit from a diagnostic work-up and preventative therapy. A few minutes directed to- ward metabolic counseling is time well spent. Patients presenting for dental implants are usually preoccupied with their masticatory problems and apprehensive about the cost of treatment. Bone metabolic counseling turns the patient’s attention from the economic con- cerns of the moment to the broader perspective of health maintenance. This unexpected benefit, provided at no additional fee, can positively influence the doctor/ patient relationship. CONCLUSIONS Bone metabolic counseling is an important health service that broadens the health perspective of the doctor/patient relationship. Assessing signs, symptoms, and risk factors for metabolie bone disease is an impor- tant consideration in diagnosis and treatment planning. ‘Skeletally compromised patients may still be acceptable candidates for dental implants assuming calcium bal- ance and other critical aspects of the metabolic disease process are controlled.20 ACKNOWLEDGMENTS, ‘This work was supported by National Institute of Dental Research (NIH) Grants DE09237 and DE09822, NASA-Ames Grant NCC 2-594, International College of Oral Implantologists and Indiana University Foun- dation. 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Liss, Inc; 1982:527-534, 43, Smith RK, Roberts WE. Cell kinetics of the initial response to orthodontically induced osteogenesis in rat molar periodontal ligament. Calif Tissue Int. 1980;30:51-56. 44. Roberts WE, Mozsary PG, Klingler E. Nuclear size as a cell-kinetic marker for osteoblast differentiation. Am J Anat. 1982;165:373-384, 45. Roberts WE, Morey ER. Proliferation and differentia: tion sequence of osteoblast histogenesis under physiological conditions in rat periodontal ligament. Am J Anat 1985;174:105-118. 46. Jackson CB, Roberts WE, Morey ER. Growth altera- tions of the mandibular condyle in Spacelab-3 rats. ASGSB. Bull. 1988;1:33. Abstract. 47, Slemenda CW, Hui SL, Longcope C, et al. Cigarette smoking, obesity, and bone mass. J Bone Miner Res. 1989;4:737-741 48. Slemenda CW, Hui SL, Longcope C, et al. Predictors fof bone mass in premenopausal women. Ann Intern Med, 1990;112:96-101. YYou'l find needed words faster! ‘Stedman's Medical Dictionary, the 25th Edition Your key? The Stedman’s Subentry Locator! This master cross-referencing guide uses adjectives to organize allmain ‘entries {nouns} by their appropriate descripives. No nu- merous and cumbersome cross-references, Your work continues smoothly because tedious look-up time is kept to en absolute minimum! What's more, only Stedman’s/25 includes: ** 10,000 new entries, over 100,000 terms ** 1,920 information-packed pages in an 8° x 10" format ** Concise definitions with simplified phonetic speling 1990/#7916-6/$41.00 a 49, Grisso JA, Baum CR, Turner BJ. What do physicians in practice do to prevent osteoporosis? JJ Bone Miner Res 1990;5:218-219, 50, Lindsay R, Tohme JF. Estrogen treatment of patients with established postmenopausal osteoporosis. Obstet Gynecol 1991;70:290-288. 51. Storm T, Thamsborg G, Steiniche T, et al. Effect of intermittent cyclical etidronate therapy on’bone mass and fracture rate in women with postmenopausal osteoporosis. V Engl J Med. 1990;322:1265-1271. 52. Riggs BL, Hodgson SF, O'Fallon M, et al. Effect of fluoride treatment on the fracture rate in’ postmenopausal women with osteoporosis. NV Engl J Med. 1990;322:802-809. 53. Roberts WE, Garetto LP, DeCastro RA. Remodeling of devitalized bone threatens periosteal margin integrity of endosseous titanium implants with threaded or smooth sur- faces: indications for provisional loading and axially directed occlusion. oJ Indiana Dent Assoc, 1989%68:19-24, 54. Roberts WE, Marshall KJ, Mozsary PG. Rigid endos- seous implant utilized as anchorage to protract molars and close an atzophie extraction site, Angle Orthod. 1990;60:135 152, Reprint requests to Dr. W. Bugene Roberts Department of Orthodontics Indiana University School of Dentistry 1121 West Michigan Street Indianapolis, IN 46202 WordPerfect spell checking ease, speed and accuracy NEW! —STEDMAN’S/25 for WordPerfect® ‘Add 150,000+ medical terms from Stedman's Medical Dictionary, 25th Ed. to WordPerfect! You get the words [AND all their aerate forms— procedures, devices, dis: eases, generictrade drug names, acronyms, and abbre- viations. It even recognizes Greek letters and diacrtical ‘markings! Easy to install. Easy to use, No additional RAM or extended ‘memory required. For WordPerfect 5.0 or later (IBM) and WordPerfect 2.01 (MACS). IBM Single User Version (#17556-4)—$99.50 (includes both 5.25" and 35" diskettes) IMAC Single User Version (##17562-9)— $9950 Call for institutional pricing and upgrade information, Call or Fax Us Toll-Free for Fast, Priority Service: Call—1-800-638-0672 Fax— 1-800-447-8438. 9. Penn STEDMANS — 428EastPresion Sueet ‘The Best Words in Medicine Baltimore. MD 21202