Pilot study comparing changes in postural control after training using a video game balance board program and 2 standard activity-based balance intervention programs.

OBJECTIVE: To compare the impacts of Tai Chi, a standard balance exercise program, and a video game balance board program on postural control and perceived falls risk. DESIGN: Randomized controlled trial. SETTING: Research laboratory. PARTICIPANTS: Independent seniors (N=40; 72.5±8.40) began the training, 27 completed. INTERVENTIONS: Tai Chi, a standard balance exercise program, and a video game balance board program. MAIN OUTCOME MEASURES: The following were used as measures: Timed Up & Go, One-Leg Stance, functional reach, Tinetti Performance Oriented Mobility Assessment, force plate center of pressure (COP) and time to boundary, dynamic posturography (DP), Falls Risk for Older People-Community Setting, and Falls Efficacy Scale. RESULTS: No significant differences were seen between groups for any outcome measures at baseline, nor were significant time or group × time differences for any field test or questionnaire. No group × time differences were seen for any COP measures; however, significant time differences were seen for total COP, 3 of 4 anterior/posterior displacement and both velocity, and 1 displacement and 1 velocity medial/lateral measure across time for the entire sample. For DP, significant improvements in the overall score (dynamic movement analysis score), and in 2 of the 3 linear and angular measures were seen for the sample. CONCLUSIONS: The video game balance board program, which can be performed at home, was as effective as Tai Chi and the standard balance exercise program in improving postural control and balance dictated by the force plate postural sway and DP measures. This finding may have implications for exercise adherence because the at-home nature of the intervention eliminates many obstacles to exercise training.

Using anthropomorphic avatars resembling sedentary older individuals as models to enhance self-efficacy and adherence to physical activity: psychophysiological correlates.

The prevalence of obesity and associated health complications are currently at unprecedented levels. Physical activity in this population can improve patient outcomes. Virtual reality (VR) self-modeling may improve self-efficacy and adherence to physical activity. We conducted a comparative study of 30 participants randomized to 3 versions of a 3D avatar-based VR intervention about exercise: virtual representation of the self exercising condition; virtual representation of other person exercising and control condition. Participants in the virtual representation of the self group significantly increased their levels of physical activity. The improvement in physical activity for participants in the visual representation of other person exercising was marginal. The improvement for the control group was not significant. However, the effect sizes for comparing the pre and post intervention physical activity levels were quite large for all three groups. We did not find any group difference in the improvements of physical activity levels and self-efficacy among sedentary, overweight or obese individuals.

Medical students' attitudes toward obese patient avatars of different skin color.

Physicians' biases for skin color and obesity may negatively affect health-care outcomes. Identification of these biases is the first step to address the problem. We randomized 128 U.S medical students into one of four animated videos of avatar physician-patient counseling sessions, varying the weight and skin color of an elderly patient avatar: white-thin, black-thin, white-obese and black-obese. Medical students viewed white obese avatars as unattractive, ugly, noncompliant, lazy, and sloppy. Medical students' comments suggested a paternalistic attitude toward avatar patients. Avatar-mediated experiences can elicit medical students' bias potentially enabling medical educators to implement bias reduction interventions.

Simulating geriatric home safety assessments in a three-dimensional virtual world.

Virtual worlds could offer inexpensive and safe three-dimensional environments in which medical trainees can learn to identify home safety hazards. Our aim was to evaluate the feasibility, usability, and acceptability of virtual worlds for geriatric home safety assessments and to correlate performance efficiency in hazard identification with spatial ability, self-efficacy, cognitive load, and presence. In this study, 30 medical trainees found the home safety simulation easy to use, and their self-efficacy was improved. Men performed better than women in hazard identification. Presence and spatial ability were correlated significantly with performance. Educators should consider spatial ability and gender differences when implementing virtual world training for geriatric home safety assessments.

Human marrow-isolated adult multilineage-inducible (MIAMI) cells protect against peripheral vascular ischemia in a mouse model.

BACKGROUND AIMS: The treatment of peripheral vascular disease (PVD) with stem cells potentially offers a promising strategy. We tested marrow-isolated adult multilineage-inducible (MIAMI) cells to induce neovascularization in a mouse model of critical hindlimb ischemia (CLI). METHODS: CLI was induced in the right hindlimb of Balb/C mice. One million MIAMI cells, normally grown at 3% O2, were injected in the adductor muscle along the ischemic region. All animals (n = 11 per group) were immunosuppressed with cyclosporine daily for the entire period. Human foreskin fibroblast (HFF) cells and phosphate-buffered saline (PBS) were used as controls. Blood perfusion in the ischemic right and non-ischemic left hindlimbs was measured. RESULTS: Compared with animals receiving HFF cells or PBS, MIAMI cells significantly improved blood perfusion, necrosis and inflammation in the ischemic limb. A fraction of injected MIAMI cells expressed CD31 and von Willebrand factor (vWF). MIAMI cells in vitro, under pro-angiogenic growth conditions, differentiated into endothelial-like cells and expressed endothelial markers such as CD31 and vWF, determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and CD31 and kinase insert domain receptor (KDR), determined by immunofluorescence. Moreover, MIAMI cells formed vascular endothelial-like tubules in the presence of matrigel. Bioplex immunoassay analysis showed increased secretion of angiogenic/anti-inflammatory factors by the MIAMI cells under 3% O2 compared with 21% O2, including monocyte chemoattractant protein-1 (MCP-1), fractalkine (Ftk), growth-related oncogene (GRO), vascular endothelial growth factor (VEGF), interleukin (IL)-6 and IL-8. Furthermore, transcripts for anti-inflammatory molecules stanniocalcin-1 (STC-1) and tumor necrosis factor-α-stimulated gene 6 (TSG-6) were up-regulated several fold. CONCLUSIONS: MIAMI cells can be very useful for patients affected by CLI. MIAMI cells promote blood vessel formation and reduce inflammation and necrosis in ischemic tissue.

Medication assessments by care managers reveal potential safety issues in homebound older adults.

BACKGROUND: Over-the-counter (OTC) medications, benzodiazepines, and barbiturates are not covered under many Medicare drug benefit plans; hence, their use by homebound older adults is largely unreported. Furthermore, the tiered design of Medicare drug formularies may in fact promote the use of older but potentially inappropriate medications. Little is known about the use of these medications in the homebound older adult population. OBJECTIVE: To determine the prevalence of the use by homebound older adults of OTC drugs, dietary supplements (vitamins, minerals, and herbal products), Part D-excluded medications (benzodiazepines and barbiturates), and potentially inappropriate medications (according to Beers criteria). METHODS: Patients were enrollees in a home and community-based Medicaid waiver provider. All clients were older than 65 and were dually eligible for Medicare and Medicaid. All clients met Florida Medicaid's medical and financial criteria for nursing home placement. The medication list was obtained by geriatric care managers during a home assessment. RESULTS: A total of 3911 older adults (mean [SD] age 83.6 [8.0] years) were taking an average of 9.9 [4.8] drugs. Of these individuals, 74.5% were using an OTC medication, 41.9% were using a dietary supplement, 29.6% were using a benzodiazepine or barbiturate, and 25.2% were using at least 1 potentially inappropriate medication. CONCLUSIONS: Based on data gathered by a geriatric care management assessment, we found that most of the homebound older adults enrolled in our study used medications not included in their Medicare drug benefit. The use of potentially inappropriate medications was also common in this population. Future drug safety initiatives involving the elderly will benefit from engaging care managers in identifying and addressing the potential hazards posed by commonly used prescribed and nonprescribed medications.

Sildenafil does not improve steady state cardiovascular hemodynamics, peak power, or 15-km time trial cycling performance at simulated moderate or high altitudes in men and women.

Sildenafil improves oxygen delivery and maximal exercise capacity at very high altitudes (≥ 4,350 m), but it is unknown whether sildenafil improves these variables and longer-duration exercise performance at moderate and high altitudes where competitions are more common. The purpose of this study was to determine the effects of sildenafil on cardiovascular hemodynamics, arterial oxygen saturation (SaO(2)), peak exercise capacity (W (peak)), and 15-km time trial performance in endurance-trained subjects at simulated moderate (MA; ~2,100 m, 16.2% F(I)O(2)) and high (HA; ~3,900 m, 12.8% F(I)O(2)) altitudes. Eleven men and ten women completed two HA W (peak) trials after ingesting placebo or 50 mg sildenafil. Subjects then completed four exercise trials (30 min at 55% of altitude-specific W (peak) + 15-km time trial) at MA and HA after ingesting placebo or 50 mg sildenafil. All trials were performed in randomized, counterbalanced, and double-blind fashion. Sildenafil had little influence on cardiovascular hemodynamics at MA or HA, but did result in higher SaO(2) values (+3%, p < 0.05) compared to placebo during steady state and time trial exercise at HA. W (peak) at HA was 19% lower than SL (p < 0.001) and was not significantly affected by sildenafil. Similarly, the significantly slower time trial performance at MA (28.1 ± 0.5 min, p = 0.016) and HA (30.3 ± 0.6 min, p < 0.001) compared to SL (27.5 ± 0.6 min) was unaffected by sildenafil. We conclude that sildenafil is unlikely to exert beneficial effects at altitudes <4,000 m for a majority of the population.

Care management and the transition of older adults from a skilled nursing facility back into the community.

After hospitalization, many older adults require skilled nursing care. Although some patients receive services at home, others are admitted to a skilled nursing facility. In the current fragmented health care system, hospitals are financially incentivized to discharge frail older adults to a facility for postacute care as soon as possible. Similarly, many skilled nursing facilities are incentivized to extend the posthospitalization period of care and to transition the patient to custodial nursing home care. The resulting overuse of institution-based skilled nursing care may be associated with various adverse medical social and financial consequences. Care management interventions for more efficient and effective skilled nursing facility use must consider the determinants involved in the decisions to admit and maintain patients in skilled nursing facilities. As we await health care reform efforts that will address these barriers, opportunities already exist for care managers to improve the current postacute transition processes.

Risk for fractures with centrally acting muscle relaxants: an analysis of a national Medicare Advantage claims database.

BACKGROUND: In older adults, both muscle relaxants and benzodiazepines are associated with sedation and cognitive impairment. Although benzodiazepines have been linked to falls and fracture injuries, no studies have examined the risk of fracture associated with muscle relaxants. OBJECTIVE: To determine whether muscle relaxants identified in the Beers criteria are associated with an increased risk of fracture injuries and to compare this risk to that with benzodiazepine use. METHODS: We conducted a case-control study using both medical and pharmacy claims data from 1.5 million enrollees in the Medicare Advantage plans of a large health maintenance organization. We matched 8164 cases of fractures with 8164 controls based on age, sex, health plan, and comorbidities. We measured the use of muscle relaxants, short-acting benzodiazepines, and long-acting benzodiazepines. Adjusted odds ratios were estimated using conditional logistic regression. RESULTS: After adjusting demographic and clinical covariates, muscle relaxants, long-acting benzodiazepines, and short-acting benzodiazepines were associated with a high risk of fracture injuries, with odds ratios of 1.40 (95% CI 1.15 to 1.72; p < 0.001), 1.9 (95% CI 1.49 to 2.43; p < 0.001), and 1.33 (95% CI 1.15 to 1.55; p < 0.001), respectively. CONCLUSIONS: An elevated risk of fracture injuries was noted among older adults using muscle relaxants. Our findings provide evidence of an association between the risk of fractures and the use of centrally acting muscle relaxants in older adults. This association supports current recommendations advising extreme caution in prescribing muscle relaxants to older adults.

Some new food for thought: the role of vitamin D in the mental health of older adults.

Vitamin D, a multipurpose steroid hormone vital to health, has been increasingly implicated in the pathology of cognition and mental illness. Hypovitaminosis D is prevalent among older adults, and several studies suggest an association between hypovitaminosis D and basic and executive cognitive functions, depression, bipolar disorder, and schizophrenia. Vitamin D activates receptors on neurons in regions implicated in the regulation of behavior, stimulates neurotrophin release, and protects the brain by buffering antioxidant and anti-inflammatory defenses against vascular injury and improving metabolic and cardiovascular function. Although additional studies are needed to examine the impact of supplementation on cognition and mood disorders, given the known health benefits of vitamin D, we recommend greater supplementation in older adults.

Optimal frequency, displacement, duration, and recovery patterns to maximize power output following acute whole-body vibration.

Power is an important component of general health, fitness, and athletic performance. Traditional overload techniques require considerable time, intensity, and volume of training. Whole-body vibration (WBV) is a potentially less time-consuming method for increasing power performance than traditional training. However, the exact protocols that can maximize power output have not yet been identified. Eleven healthy men, aged 32.3 +/- 4.1 years, and 9 healthy women, aged 29.1 +/- 3.5 years, performed countermovement jumps (CMJs) of maximal volition to assess peak power pre and post (immediately and at 1, 5, and 10 minutes) randomized WBV stimuli set at different frequency (30, 35, 40, and 50 Hz), displacement (2-4 vs. 4-6 mm), and duration (30, 45, and 60 seconds) combinations. Repeated-measures analysis of variance on peak power normalized to initial power (nPP) revealed no significant effects attributable to duration of stimulus. However, high frequencies were more effective when combined with high displacements, and low frequencies were more effective in conjunction with low displacements (p < 0.05). Additionally, the greatest improvements in nPP occurred at 1 minute posttreatment, with significant improvements lasting through 5 minutes posttreatment (p < 0.05). Optimal acute effects can be attained using as little as 30 seconds of WBV, and they are highest from 1 to 5 minutes posttreatment. Additionally, high frequencies were most effective when applied in conjunction with high displacements, whereas low frequencies were most effective when applied in conjunction with low displacements.

Displacement and frequency for maximizing power output resulting from a bout of whole-body vibration.

Whole-body vibration (WBV) has been shown to be effective for increasing lower-body power; however, the combination of frequency, displacement, and duration that elicits the best acute response has yet to be determined. The purpose of this study was to identify the protocol eliciting the greatest improvement in power after an acute bout of WBV. Forty men and women participated in this study, in which 8 different combinations of 30, 35, 40, and 50 Hz with 2-mm and 5-mm displacements were tested over 3 days. For all protocols, randomized to reduce potential order effects, subjects underwent 30 seconds of WBV while holding an isometric squat at a knee angle of 2.27 rad. Power was assessed by countermovement jumps. Subjects performed 3 jumps before WBV, immediately afterward, and 1, 5, and 10 minutes later. The highest normalized peak power (nPP) at each time point was determined using a 4 (frequency) x 2 (displacement) x 5 (time) repeated-measures analysis of variance. Significant effects were seen for frequency (p < or = 0.026) and time (p < or = .0001). Post hoc analyses revealed that the 30-Hz condition (1.010 +/- 0.003) produced a higher nPP than 35 Hz (1.00 +/- 0.003, p < or = 0.026) and 40 Hz (1.002 +/- 0.002, p < or = 0.028) but not 50 Hz (1.004 +/- .002). We also found a significantly higher nPP for the 1-minute post-treatment time point (1.011 +/- .0003) vs. all other time points (p < or = 0.006). Our data show that an acute WBV bout can significantly increase power output at 1 minute post-treatment across all frequencies and displacements, although 30 Hz appears to have a greater effect on power output than either 35 Hz or 40 Hz, but not 50 Hz, at all post-treatment time points.

Computer-based animations and static graphics as medical student aids in learning home safety assessment: a randomized controlled trial.

BACKGROUND: Although animations may intuitively seem more effective than static graphics for teaching, there is no clear-cut evidence for the superiority of simple computer-based animations in medical education. AIMS: We investigated whether simple animations are better than static graphics as an aid to medical students in learning home safety assessment, an important part of geriatric curriculum. METHODS: We used two versions of an interactive online module, one that depicted common home safety issues in static graphics and the other in animations. We randomized first-year medical students who agreed to participate into two groups. After the module, students completed a cognitive burden scale and a standardized competency assessment test in which they had to identify the salient home safety issues and give recommendations based on the hazards. We also captured time spent on task. RESULTS AND CONCLUSIONS: We found no significant differences between the groups in the cognitive burden level, competency assessment scores, and time spent on task. The much cheaper-to-produce static graphics were equally effective as simple animations in this medical education scenario.

The ramp power test: a power assessment during a functional task for older individuals.

BACKGROUND: Power is critical to mobility and activities of daily living and is a key determinant of independence and falls prevention. Therefore, the quantification of power in older persons is critical. The power tests currently available are often expensive, potentially dangerous, and not reflective of everyday activities. We present a modification of an existing field test that uses ambulation up a standard access ramp to quantify functional power in older individuals. METHODS: Three hundred sixty-three women and 157 men, aged 73.1 +/- 7.0 years, ambulated up a standard access ramp (1:12 rise/run ratio) as quickly as possible. Each person performed one practice and two timed trials. RESULTS: Comparisons with accepted power measures and reported patterns of change with aging supported the validity of the ramp power test. The test was found to be reliable across multiple trials and days. Pair-wise comparisons showed that for women the test was sensitive to differences in power output by half-decade, whereas for men it could distinguish between 9 of the 15 comparisons among age groups. Percentile scores are reported by half-decade for power in both genders. In > 1200 trials performed during this study, only one injury (a slightly strained hamstring) occurred. CONCLUSIONS: The ramp power test is valid and reliable and can safely distinguish power by half-decade in women and among the majority of age groups in men. Its safety, low cost, and ease of administration make it a feasible diagnostic tool to assess functional power levels in ambulatory older persons.

Care coordination and telemedicine improves glycaemic control in ethnically diverse veterans with diabetes.

We conducted a pilot study of a care-coordination programme involving daily monitoring and education of elderly diabetic veterans from different racial/ethnic groups. A telephone-based, in-home messaging device was used for patient monitoring and education. Sixty-nine patients were enrolled in the study and HbA(1c) values were obtained both before and after the telemedicine intervention in 41 of them. The mean HbA(1c) before enrolment was 7.6% and the mean value 9 months later was 7.3% (P = 0.09). The greatest fall in HbA(1c) occurred in African-Americans (0.65%, P = 0.05). The total number of hospital admissions decreased from 31 pre-enrolment to 25 post-enrolment (P = 0.0002). Bed days of care decreased from 368 to 149 (P = 0.0002). Care coordination, facilitated by telemedicine, appeared to improve glycaemic control in veterans with diabetes from diverse ethnic backgrounds, particularly African-Americans. This may reduce health-care resource utilization.

Low oxygen tension inhibits osteogenic differentiation and enhances stemness of human MIAMI cells.

We recently reported the isolation of a unique subpopulation of human stromal cells from bone marrow (BM) termed marrow-isolated adult multilineage inducible (MIAMI) cells, capable of differentiating in vitro into mature-like cells from all three germ layers. The oxygen tension (pO2) in BM ranges from 1 to 7%, which prompted us to examine the role of pO2 in regulating the capacity of MIAMI cells both to self-renew and maintain their pluripotentiality (stemness) or to progress toward osteoblastic differentiation. MIAMI cells were grown under low-pO2 conditions (1, 3, 5, and 10% oxygen) or air (21% oxygen). The proliferation rate of cells exposed to 3% oxygen (3 days) increased, resulting in cell numbers more than threefold higher than those of cells exposed to air (at 7 days). In cells grown under osteoblastic differentiation conditions, the expression of the osteoblastic markers osteocalcin, bone sialoprotein, osterix, and Runx2 and alkaline phosphatase activity was upregulated when incubated in air; however, it was blocked at low (3%) pO2. Similarly, biomineralization of long-term cell cultures was high under osteoblastic differentiation conditions in air but was undetectable at low (3%) pO2. In contrast, low pO2 upregulated mRNAs for OCT-4, REX-1, telomerase reverse transcriptase, and hypoxia-inducible factor-1 alpha, and increased the expression of SSEA-4 compared to air. Moreover, the expression of embryonic stem cell markers was sustained even under osteogenic culture conditions. Similar results were obtained using commercially available marrow stromal cells. We hypothesize a physiological scenario in which primitive MIAMI cells self-renew while localized to areas of low pO2 in the bone marrow, but tend to differentiate toward osteoblasts when they are located closer to blood vessels and exposed to higher pO2. Our results strongly suggest that maintaining developmentally primitive human cells in vitro at low pO2 would be more physiological and favor stemness over differentiation.

Sustained stromal stem cell self-renewal and osteoblastic differentiation during aging.

We have reported the isolation of a unique subpopulation of human stromal cells from bone marrow termed marrow-isolated adult multilineage inducible (MIAMI) cells. The expression of embryonic stem cell markers SSEA-4, Oct-4, Rex-1, and telomerase reverse transcriptase indicates the developmentally immature status of these cells. They resemble primitive stem cells in their capacity to differentiate, at least in vitro, into mature-like cells from all three germ layers. MIAMI cells are characterized by a unique molecular profile that distinguishes them from other marrow stromal cell populations. Although the frequency of MIAMI cells, among all marrow nucleated cells, decreases from 0.01% at age 3 to 0.0018% at age 45, their numbers remain unchanged after age 45. The level of expression of the markers characteristic of MIAMI cells remains constant independent of age and gender. In long-term in vitro expansion experiments aging increased the population doubling time by about 30%, whereas specific in vitro differentiation of MIAMI cells toward osteoblastic cells was unaffected. Because the oxygen tension in bone marrow ranges from 1% to 7%, we examined the role of oxygen tension in regulating the capacity of MIAMI cells to self-renew and maintain their pluripotentiality during long-term culture. Low oxygen tension upregulated mRNAs for primitive embryonic stem cell markers. Our results suggest that maintaining developmentally primitive human cells in vitro at low oxygen tension is more physiologic and favors stemness. For osteoblastic differentiation, gap-junctional communication mediated by connexin43 is required. Its inhibition not only blocked osteoblastic differentiation but stimulated the adipocytic differentiation.

Vitamin d deficiency and seasonal variation in an adult South Florida population.

Hypovitaminosis D is associated with impaired neuromuscular function, bone loss, and fractures. If a person is not taking a vitamin supplement, sun exposure is often the greatest source of vitamin D. Thus, vitamin D deficiency is not uncommon in the winter, particularly in northern latitudes. Our goal was to establish the prevalence of vitamin D deficiency in south Florida (U.S.), a region of year-round sunny weather. At the end of the winter, 212 men and women attending an internal medicine clinic at a local county hospital were enrolled for measurements of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, and PTH; 99 participants returned at the end of summer. The mean (+/-sd) winter 25(OH)D concentration was 24.9 +/- 8.7 ng/ml (62.3 +/- 21.8 nmol/liter) in men and 22.4 +/- 8.2 ng/ml (56.0 +/- 20.5 nmol/liter) in women. In winter, the prevalence of hypovitaminosis D, defined as 25(OH)D less than 20 ng/ml (50 nmol/liter), was 38% and 40% in men and women, respectively. In the 99 subjects who returned for the end of summer visit, the mean 25(OH)D concentration was 31.0 +/- 11.0 ng/ml (77.5 +/- 27.5 nmol/liter) in men and 25.0 +/- 9.4 ng/ml (62.5 +/- 23.5 nmol/liter) in women. Seasonal variation represented a 14% summer increase in 25(OH)D concentrations in men and a 13% increase in women, both of which were statistically significant. The prevalence of hypovitaminosis D is considerable even in southern latitudes and should be taken into account in the evaluation of postmenopausal and male osteoporosis.

Early plateaus of power and torque gains during high- and low-speed resistance training of older women.

Periodization is the most effective approach to resistance training; however, optimal cycle lengths for older persons are not known. This study examined the durations of performance increments, plateaus, and decrements in women, ages 61-75 yr, over 9 wk of isokinetic training. After a 2-wk adaptation cycle, older women trained for either power (PWR; 4.73 rad/s; n = 9) or strength (STR; 1.05 rad/s; n = 8), 3 days/wk with a 1-day recovery between sessions. Repetitions were initially selected to equilibrate work volume between groups. Average power (AP), peak torque (PT), and total work (TW) curves were analyzed using forward and backward stepwise regression to ascertain inflections and plateaus. PWR training produced the highest AP, whereas STR produced the highest PT. TW was similar between groups. The AP curves of the PWR group initially showed a steep positive slope and then plateaued during week 3. The right leg plateau lasted throughout training, whereas the left leg showed another positive inflection during weeks 7 and 8. PWR group TW curves showed positive slopes throughout training. STR group PT curves for both legs showed initial positive slopes peaking between weeks 3 and 4 and declining thereafter. The TW curves for both legs showed slight negative slopes across the first 2 wk, steep positive slopes during weeks 3-6, and a final plateau. Because improvements plateau early during PWR and STR training, isokinetic training prescriptions for optimizing strength and power improvements in older persons should use cycles of 3-4 wk to maximize gains.

Autosomal dominant hyperostosis/osteosclerosis with high serum alkaline phosphatase activity.

We studied eight affected and four unaffected individuals from a Colombian family with autosomal dominant diffuse high bone density. Affected individuals have normal, proportional height and high serum alkaline phosphatase activity. Radiographically, affected members exhibit generalized, symmetrically diffuse endosteal hyperostosis of the long bones and skull with narrow medullary cavities and loss of the diploë, respectively. There is no periosteal reaction or decreased hematopoiesis. Furthermore, osteosclerosis affects vertebral bodies, ribs, pelvis, mandible, clavicles, and scapulae. Bone mineral density is 2.4-7.3 SD above the mean for age and gender in affected individuals. Affected vs. unaffected individuals' Z-scores were (mean +/- SD) 5.03 +/- 1.77 vs. 0.08 +/- 0.97, respectively, P = 0.0004). Three affected subjects older than 40 yr old lost bone mass in 6 yr. No dysmorphism, abnormal facial features, bone fractures, or cranial nerve involvement was found. The pattern of inheritance, the absence of asymmetries and malformations, the increased serum alkaline phosphatase, the peak bone mass that appears to decrease physiologically with age, and the involvement of cortical and trabecular bone suggest a new variant of hyperostosis/osteosclerosis that affects the entire skeleton.