The Otto Aufranc Award. Skeletal response to well fixed femoral components inserted with and without cement

Previous studies evaluating femoral remodeling after total hip arthroplasty have used clinical radiographs and dual energy xray absorptiometry. Limitation of these techniques make it impossible to quantify the magnitude of bone loss in terms of cortical thinning and cortical bone area and bone mineral density changes. Femoral cortical bone remodeling after cemented and cementless replacement was quantified and possible determinants of bone remodeling in terms of clinical and radiographic variables were evaluated. Forty-eight anatomic specimen femora from 24 patients with unilateral cemented and cementless hip replacements were analyzed. Cortical thickness, cortical bone area, and bone mineral density was assessed in 4 quadrants at 5 discrete levels. The maximum cortical bone loss by level was at the middle section for the cemented femurs and at the midproximal and middle sections for the cementless femurs. However, if one examines individual quadrants, the proximal medial cortex still represents the specific region of maximal bone loss for both types of implant fixation. The posterior cortex had substantially more bone loss, even in the diaphyseal levels, than had been previously appreciated. A strong correlation was noted between the bone mineral density of the control femur and the percentage decrease of bone mineral density in the remodeled femur. Based on this data, it seems that the less dense the bone is before hip replacement surgery, the greater the extent of bone loss after total hip arthroplasty regardless of the fixation type.     

The influence of clinical factors on periprosthetic bone remodeling

The femurs of 11 patients with well-functioning unilateral hip replacements were retrieved at autopsy and analyzed for periprosthetic bone remodeling by dual energy xray absorptiometry. Each case involved a femur with a porouscoated endoprosthesis; the endoprosthesis remained implanted for an average of 5.9 years. In the contralateral femur, a matching prosthesis was implanted in vitro, to serve as a control for comparisons. There was an average 22.6% decrease in bone mineral content in the in vivo implanted femur (range, 5.4%-47.4%). Females experienced an average bone loss of 31.2%, which was significantly higher than the 12.3% average loss in males. Longitudinal analysis revealed an average decrease in bone mineral content of 42.1% proximally, 23% in the midsection, and 5.5% distally. Percent decreases in total bone mineral content were correlated with the following clinical variables: weight, age, implant diameter, duration of implantation, and contralateral femoral bone mineral content. Only the bone mineral content of the contralateral femur had a strong predictive value. Bone loss was greater in femurs with low bone mineral content than in those with high bone mineral content. Weight, age, implant diameter, and duration of implantation were not correlated with bone loss.     

A prospective study of bone loss in African-American and white women--a clinical research center study

Although bone loss occurs universally with age, the incidence of age-related osteoporotic fractures varies widely among ethnic groups. In the U.S., age-adjusted hip fracture incidence is 50% lower in African-American than in white women. Adult African-American women also have higher bone mass, but it is not known whether this difference is entirely due to higher peak bone mass or also results from slower rates of bone loss. Rates of bone loss were measured prospectively in 122 white and 121 African-American healthy, nonobese, pre- and postmenopausal women. Bone density was measured at 6-month intervals over a mean of 3-4 yr using single and dual photon absorptiometry of the forearm (cortical bone) and spine (trabecular bone). Similar rates of premenopausal bone loss were documented in both white and African-American women. However, in early menopause, bone loss was faster in the white women in the forearm (-2.4%/yr in whites vs. -1.2%/yr in African-Americans; P = 0.045), with a similar trend in the spine (-2.2%/yr in whites vs. -1.3/yr in African-Americans; P = 0.27). In women more than 5 yr postmenopause, the rates of bone loss did not differ by ethnic group. Our results indicate that the higher bone mass in African-American women is largely due to the attainment of a greater peak bone mass by early adulthood. However, slower rates of bone loss in the early postmenopausal period may also contribute to the higher bone density of older African-American women. Although bone loss occurs in both groups, there are ethnic differences in bone loss rates which indicate that data derived from white women cannot be simply extrapolated to nonwhite populations. Ethnic group-specific data on the determinants of bone homeostasis are needed.     

Evaluation of periprosthetic bone using dual-energy x-ray absorptiometry: precision of the method and effect of operation on bone mineral density

To assess the perioperative bone loss of femur during total hip arthroplasty (THA), periprosthetic bone mineral density (BMD) of the seven regions of interests (Gruen zones) was determined with dual-energy x-ray absorptiometry (DXA) preoperatively in both proximal femurs and postoperatively in the involved side in 53 patients with degenerative hip osteoarthrosis. The mean (standard deviation, SD) precision error (coefficient of variation percent, CV%) in various regions of interest (ROIs) based on two consecutive measurements (n = 16) were 2.3 (0.8)%, 2.5 (1.5)%, and 2.8 (1.6)% for uncemented stems, cemented stems, and control sides, respectively. Furthermore, the mean variability caused by the rotation of femur was 3.5 (1.4)%. The most significant perioperative bone loss (13.5-19.2%) was found in the calcar area (zone 7) after noncemented THA. Zone 4, representing the bone below the prosthesis, also showed BMD decreases. These decreases suggest perioperative bone loss owing to rasping and reaming the calcar and bone canal. However, after cemented THA, highly significant BMD increases were found in all the lateral zones. The calcar area was the only site where significant perioperative bone loss was detected (12.8%). In conclusion, DXA is a precise method for quantifying bone mass and density changes in the follow-up of THA. However, when interpreting the results, the preoperative BMD, differences between the femurs and the effect of operation on bone mass should be taken into account. We suggest that the best reference for BMD follow-up is the periprosthetic BMD of the involved side measured soon after the THA.     

Polymer concepts in tissue engineering

Dual energy x-ray absorptiometry (DXA) allows the measurement of bone mineral density (BMD) around an uncemented hip prosthesis. The aims of this study were: 1) to determine the reproducibility of periprosthetic BMD measurements; 2) to delineate the time course of bone loss that occurs after insertion of a hip prosthesis; and 3) to compare the bone loss around two different types of hip prosthesis. We studied 20 patients: 11 had Bateman and 9 had porous-coated anatomic prostheses inserted. The mean bone loss in 20 patients between 6 and 52 weeks after surgery was 6%. The greatest loss during this period was 18% and occurred from the proximal medial cortex. We conclude that measurement of periprosthetic bone mass by DXA is a precise technique. Bone loss was rapid in the first 6 months following total hip replacement. There was no difference in the bone loss occurring around the two prostheses studied.     

Dual-energy X-ray absorptiometry in osteonecrosis of the femoral head

Osteonecrosis of the hip classically produces a heterogeneous density in the femoral head, although the bone marrow ischemia extends down to the femoral neck and trochanters. Also, bone insufficiency fractures due to diffuse bone loss have been implicated in the genesis of osteonecrosis. OBJECTIVES: To use dual-energy X-ray absorptiometry to quantify the bone changes produced by osteonecrosis of the hip and to compare bone mineral density values in patients with osteonecrosis of the hip and in controls. METHODS: Bone mineral density was measured at the femoral neck (total femoral neck, Ward's triangle, and trochanter), femoral head and lumbar spine using dual-energy X-ray absorptiometry (DPX, L Lunar) in 22 patients with osteonecrosis of the hip and in 22 age- and sex-matched controls. RESULTS: In the patients with osteonecrosis, bone mineral density on the affected side was higher than on the opposite side at the femoral head (+18%), femoral neck (+7%), and Ward's triangle (+6%) and lower at the trochanter (-4%). These differences were most marked at the more advanced end of the osteonecrosis spectrum. As compared to age-specific normative values, the osteonecrosis patients had moderately decreased bone mineral density values at the lumbar spine (-0.53 +/- 1.1 SD or -6 +/- 1.5%) and at the femoral neck on the normal side (-0.9 +/- 1.4 SD or 12 +/- 1.8%). As compared to the controls, bone mineral density was significantly decreased at Ward's triangle (-25%; P: 0.04) and nonsignificantly decreased at the lumbar spine (-4.7%; P: 0.15) and at the femoral neck (-15%; P: 0.09).     

Bone densitometry: patients receiving prolonged steroid therapy

Bone mass loss and osteoporosis are associated with various conditions, such as asymptomatic primary hyperparathyroidism, and treatments, such as prolonged steroid therapy. Bone densitometry is used to measure bone mass density to determine the degree of osteoporosis and to estimate fracture risk. Bone densitometers measure the radiation absorption by the skeleton to determine bone mass of the peripheral, axial, and total skeleton. Common techniques include single-photon absorptiometry (SPA) of the forearm and heel, dual-photon (DPA) and dual-energy x-ray absorptiometry (DXA) of the spine and hip, quantitative computed tomography (QCT) of the spine or forearm, and radiographic absorptiometry (RA) of the hand. Part I of this report addresses important technical considerations of bone densitometers, including radiation dose, site selection, and accuracy and precision, as well as cost and charges. Part II evaluates the clinical utility of bone densitometry in the management of patients receiving prolonged steroid therapy. Steroids have broad effects on both immune and inflammatory processes and have been used to treat a wide variety of immunologically mediated diseases. Osteoporosis and vertebral compression fractures have been considered major complications of prolonged steroid therapy. Bone loss is also a direct result of many of the diseases treated with steroids. Issues addressed are the type and extent of bone loss associated with steroid therapy, risk for fracture, whether steroid dose reduction or alternative therapy is an option, and whether osteoporosis associated with prolonged steroid use can be prevented or treated. The other assessments in this series address the clinical utility of bone densitometry for patients with: asymptomatic primary hyperparathyroidism, end-stage renal disease, vertebral abnormalities, and estrogen-deficient women.     

Correlation of computed finite element stresses to bone density after remodeling around cementless femoral implants

Fundamental to the development of a durable, uncemented femoral component is an understanding of the remodeling process that goes on after implantation. Predicting the bone remodeling that results from the use of a given hip implant would facilitate the design of a prosthesis that would optimize bone adaptation. This report combines the results of finite element stress analysis of the AML prosthesis implanted in vitro into a proximal femur with quantitative bone mineral density measured in vivo in the medial and lateral aspects of human femora at periods after implantation. Unimplanted femora were also analyzed for comparison purposes. Bone density measurements were obtained using dual energy x-ray absorptiometry. Absolute values of the maximum principal stress and maximum shear stress calculated in the femur at the time of implantation accurately predict bone density resulting from remodeling caused by the prosthesis. The calculated initial strain was not found to correlate with resultant bone density. These findings suggest that the results of stress analyses using three dimensional models of femora implanted in vitro can predict bone remodeling around prostheses and may be used to quantitate appropriate design criteria for total hip replacements.     

Accelerated hyperfractionated radiotherapy combined with induction and concomitant chemotherapy for inoperable non-small-cell lung cancer--impact of total treatment time

PURPOSE: To determine the importance of fall characteristics, body habitus, function, and hip bone mineral density as independent risk factors for hip fracture in frail nursing home residents. SUBJECTS AND METHODS: In this prospective, case-control study of a single, long-term care facility, we enrolled 132 ambulatory residents (95 women and 37 men) aged 65 and older, including 32 cases (fallers with hip fracture) and 100 controls (fallers with no hip fracture). Principal risk factors included fall characteristics, body habitus, measures of functional assessment, and hip bone mineral density by dual-energy X-ray absorptiometry. RESULTS: In multivariate analysis, including only those with knowledge of the fall direction (n=100), those who fell and suffered a hip fracture were more likely to have fallen sideways (odds ratio 5.7, 95% confidence interval [CI] 1.7 to 18, P= 0.004) and have a low hip bone mineral density (odds ratio 1.9, 95% CI 0.97 to 3.7, P=0.06) than those who fell and did not fracture. When all participants were included (n=132) and subjects who did not know fall direction were coded as not having fallen to the side, a fall to the side (odds ratio 3.9, 95% CI 1.3 to 11, P=0.01), low hip bone density (odds ratio 1.8, 95% CI 1.03 to 3, P=0.04), and impaired mobility (odds ratios 6.4, 95% CI 1.9 to 21, P=0.002) were independently associated with hip fracture. Sixty-seven percent of subjects (87% with and 62% without hip fracture) had a total hip bone mineral density greater than 2.5 SD below adult peak bone mass and were therefore classified as having osteoporosis using World Health Organization criteria. CONCLUSIONS: Among frail elderly nursing home fallers, the preponderance of whom are osteoporotic, a fall to the side, a low hip bone density, and impairment in mobility are all important and independent risk factors for hip fracture. These data suggest that, among the frailest elderly, measures to reduce the severity of a sideways fall and improve mobility touch on new domains of risk, independent of bone mineral density, that need to be targeted for hip fracture prevention in this high-risk group.     

Aerobic workout and bone mass in females

This cross-sectional study aimed to investigate bone mass in females participating in aerobic workout. Twenty-three females (age 24.1 +/- 2.7 years), participating in aerobic workout for about 3 hours/week, were compared with 23 age-, weight- and height-matched non-active females. Areal bone mineral density (BMD) was measured in total body, head, whole dominant humerus, lumbar spine, right femoral neck, Ward's triangle, trochanter femoris, in specific sites in right femur diaphysis, distal femur, proximal tibia and tibial diaphysis, and bone mineral content (BMC) was measured in the whole dominant arm and right leg, using dual energy X-ray absorptiometry. The aerobic workout group had significantly (P < 0.05-0.01) higher BMD in total body (3.7%), lumbar spine (7.8%), femoral neck (11.6%), Ward's triangle (11.7%), trochanter femoris (9.6%), proximal tibia (6.8%) and tibia diaphysis (5.9%) compared to the non-active controls. There were no differences between the groups concerning BMD of the whole dominant humerus, femoral diaphysis, distal femur and BMC and lean mass of the whole dominant arm and right leg. Leaness of the whole dominant arm and leg was correlated to BMC of the whole dominant arm and right leg in both groups. In young females, aerobic workout containing alternating high and low impact movements for the lower body is associated with a higher bone mass in clinically important sites like the lumbar spine and hip, but muscle strengthening exercises like push-ups and soft-glove boxing are not associated with a higher bone mass in the dominant humerus. It appears that there is a skeletal adaptation to the loads of the activity.     

Biomechanical and densitometric bone properties after callus distraction in sheep

Assessment of biomechanical stability of diaphyseal bone lengthened by callus distraction is an unsolved problem. A middiaphyseal corticotomy was performed in the left tibia of 24 sheep. After 7 days, callus distraction was begun at a rate of 0.5 mm every 12 hours for 30 days using a standard unilateral fixator system. Animals were euthanized 4, 8, or 12 weeks after the end of distraction. The lengthened tibia and the contralateral control tibia from each animal were evaluated by radiographic, densitometric (dual energy xray absorptiometry, quantitative computed tomography), and biomechanical (axial compression testing, torsion testing to failure) methods. The bone mineral density and maximum torque for the lengthened tibia were significantly greater in the 8-week group than in the 4-week group. However, the values in the 12-week group were significantly smaller than in the 8-week group. In the lengthened tibias, there was a correlation between the maximum torque and the bone mineral density, and between the maximum torque and the bone density. Bone density measurements are useful prognosticators for the safe removal of external fixators after leg lengthening procedures. By using these methods, clinical fractures after leg lengthening could be avoided in the future.     

Bone loss associated with a high fibre weight reduction diet in postmenopausal women

OBJECTIVE: To examine the effect of high fibre weight reduction on bone density in postmenopausal women. DESIGN: Case-control study. SETTING: Hospital outpatient dietetic clinic and Osteoporosis Screening Unit. SUBJECTS AND INTERVENTIONS: Sixteen overweight volunteers who followed a high fibre reducing diet for 6 months, to lose 20% of excess body weight (above body mass index 25 kg/m2), and returned to their starting weight by the end of a further 6 months. Forty-six non-dieting controls, matched for age and years postmenopause, selected from screening unit volunteer register. RESULTS: Annual percentage changes in lumbar spine bone mineral density, measured by dual energy X-ray absorptiometry were: controls -2.5% (SE 0.5), dieters -4.8% (0.9), 95% confidence interval of difference between groups -0.2 to -4.3% (P = 0.03); femoral neck bone density controls -2.5% (0.5), dieters -2.1% (0.9), 95% confidence interval of difference -1.7 to 2.5% (P = 0.69). CONCLUSIONS: High fibre weight reduction in postmenopausal women significantly increased annual bone loss from the lumbar spine. This loss was not reversed by weight regain in the second 6 months. Repeated cycles of high fibre weight loss and weight gain may increase the risk of spinal osteoporosis.     

Structural allograft in two-stage revisions for failed septic hip arthroplasty

We report 11 patients having revision of total hip arthroplasty using massive structural allografts for failure due to sepsis and associated bone loss. All patients had a two-stage reconstruction and the mean follow-up was 47.8 months (24 to 72). Positive cultures were obtained at the first stage in nine of the 11 patients, with Staphylococcus epidermidis being the most common organism. The other two patients had draining sinuses with negative cultures. There was no recurrence of infection in any patient. The mean increase in the modified Harris hip score was 45 and all the grafts appeared to have united to host bone. Two patients required additional procedures, but only one was related to the allograft. Complications included an incomplete sciatic nerve palsy and one case of graft resorption. Our results support the use of massive allografts in failed septic hip arthroplasty in which there is associated bone loss.     

Assessment of bone in Ehlers Danlos syndrome by ultrasound and densitometry

OBJECTIVE: Ehlers Danlos syndrome (EDS) is an inherited disorder of connective tissue characterised by hyperextensible skin, joint laxity, and easy bruising. There are phenotypic similarities with osteogenesis imperfecta, but in EDS a tendency to fracture or altered bone mass has not previously been considered to be a cardinal feature. METHOD: This case-control design study investigates whether 23 patients with EDS had differences in fracture rates, bone mass, and calcaneal ultrasound parameters compared with age and sex matched controls. RESULTS: 23 cases of EDS (mean (SD) age 38.5 (15.5)) were compared with 23 controls (mean age 37.8 (14.5)). A significant reduction in bone density measured by dual energy x ray absorptiometry was found at the neck of femur by 0.9 SD, p = 0.05, and lumbar spine by 0.74 SD, p = 0.02. At the calcaneum, broad band ultrasound attenuation and speed of sound were significantly reduced compared with controls by 0.95 SD (p = 0.004) and 0.49 SD (p = 0.004) for broad band ultrasound attenuation and speed of sound respectively. Broad band ultrasound attenuation and speed of sound remained significantly reduced after adjusting for bone mineral density (BMD). After adjusting for functional status (HAQ), age and sex, hypermobility was inversely correlated with broad band ultrasound attenuation and SOS, but not BMD at hip or spine. Previous fracture was 10 times more common in EDS (p < 0.001), with 86.9% of patients reporting a total of 47 low impact fractures, compared with 8.7% of controls. CONCLUSION: This study has identified a tendency of EDS patients to fracture, have low bone mass and abnormal bone structure. The aetiology is likely to be multifactorial, with an inherited structural element, accentuated by immobility or reduced exercise. This is one of the first clinical studies to suggest ultrasound can detect structural differences in bone, independent of dual energy x ray absorptiometry.     

Relationships between bone mass measurements and lifetime physical activity in a Swedish population

Lifetime occupational and leisure time activities were assessed by a questionnaire in order to evaluate their relationship to bone mass measurements and biochemical markers of bone metabolism in a population of 61 women and 61 men, randomly selected from a Swedish population register, to represent ages between 22 and 85 years. We also considered possible confounders by using questions about smoking habits, milk consumption, hormone replacement therapy (HRT), and menopausal age. Bone mineral density (BMD) and bone mineral content (bone mass, BMC) of the total body, lumbar spine, and proximal femur (neck, trochanter, Ward's triangle) were measured by dual energy X-ray absorptiometry (DXA), and BMD of the forearm with single energy X-ray absorptiometry (SXA). In addition, both DXA and SXA provided information on bone area. Quantitative ultrasound measurements (QUS) at the heel were performed to assess the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Fasting blood samples were analyzed for biochemical markers of bone metabolism as well as parathyroid hormone (PTH) and total serum calcium. After adjustment for confounding factors, neither BMD nor QUS measurements were consistently related to lifetime leisure time or occupational activities; nor were there any consistent patterns relating biochemical markers of bone metabolism to bone mass measurements. However, physical activity seemed to influence bone mass, area, and width more than density. In men, high levels of leisure time activity were associated with raised values for lumbar spine area (6.2%) and width (3.3%) as well as for femoral neck area (5.5%) compared with their low activity counterpart. Men exposed to high levels of occupational activity demonstrated lower lumbar spine BMD (10.9%) and area (5.3%) than men with low activity levels. Within an unselected Swedish population, estimation of lifetime occupational and sport activities as well as bedrest, using a questionnaire, demonstrated no major effects on bone density. However, the association between high levels of lifetime activity and raised values for bone mass, area, and width indicate that geometrical changes in bone may provide better estimations of mechanically induced bone strength than bone density, at least in men.     

Aspirin therapy for cardiovascular disease

Bone densitometry has become a major tool for osteoporosis risk assessment. The traditional dual-energy X-ray absorptiometry (DXA) methods are able to evaluate the bone mineral content (BMC; mg/cm) and the areal density (BMD; mg/cm2), but only quantitative computed tomography (QCT) has the potential to measure the true volumetric bone density in the sense of mass per unit volume (mg/cm3). Peripheral QCT (pQCT) measurements were carried out at the nondominant radius using a Stratec XCT 960 (Unitrem, Roma) in 241 postmenopausal and 29 premenopausal women. The sites of evaluation were both the ultradistal and the proximal radius. The technique used has a coefficient of variation of 2% and it allows separation of the bone section into trabecular and cortical bone on the basis of density threshold. Bone mass of radius, hip and spine was also evaluated by DXA procedures. The bone density data obtained by pQCT were significantly correlated with all DXA measurements. The correlation coefficients between their respective BMD values ranged from 0.48 to 0.75, but for the BMC values of the radius the correlation coefficients ranged from 0.82 to 0.93. The BMD values measured by DXA, but not by pQCT, were positively related with patient heights. All pQCT density measurements, including those obtained at the proximal radius and containing exclusively cortical bone, where negatively related with age and years since menopause. A partial volume effect, which is increasingly relevant the thinner are the bone cortices, might explain that. However, by applying increasing density thresholds, cortical bone density seems to decrease with age as a consequence of a gradual density diminution from the inner part of the bone cortex outwards. Trabecular bone density decreases with aging, but its overall mass does not change as a consequence of an age-related enlargement of trabecular area. Thus, the proportion of trabecular bone over total bone rises, and this might be relevant for our understanding of the age-related changes in bone turnover and rate of bone loss.     

Urinary bombesin-like peptide levels in infants and children with bronchopulmonary dysplasia and cystic fibrosis

OBJECTIVE: Changes in body composition during a weight loss program have not been described in children. We wanted to test the hypothesis that weight loss can be achieved while maintaining total body fat-free mass. RESEARCH METHODS AND PROCEDURES: We determined body composition changes by using dual-energy X-ray absorptiometry measured at baseline and after the first 10 weeks of a multidisciplinary weight loss program. The program consisted of 10 weekly group sessions where the children were provided instruction in lifestyle modification, including diet and exercise. Program leaders included a pediatrician, psychologist, registered dietitian, and exercise instructor. RESULTS: We studied 59 obese children, mean (+/-SD) age 12.8+/-2.6 years, 29% boys and 71% girls, 49% Caucasian, and 51% African American. At enrollment, the children's mean height and body mass index were 157 cm and 38.9 kg/m2, respectively. The children's dual-energy X-ray absorptiometry-derived mean at baseline and at 10 weeks and corresponding p values were: weight (94.6 kg vs. 92.3 kg, p<0.0001), total body fat mass (46.9 kg vs. 44.3 kg, p<0.0001), percentage total body fat (49.2% vs. 47.5%, p<0.0001), total trunk mass (43.0 kg vs. 41.5 kg, p<0.0001), total trunk fat (21.2 kg vs. 20.0 kg, p<0.0001), total body fat-free mass (47.6 kg vs. 47.9 kg, p=0.33), total body bone mass (2.7 kg vs. 2.7 kg, p=0.99), and total body bone mineral density (1.14 g/cm2 vs. 1.15 g/cm2, p=0.0119). The children's race, gender, or Tanner stage did not affect these changes. DISCUSSION: Decreases in total body fat mass was achieved, and total body fat-free mass was maintained among boy and girl Caucasian and African American children participating in this lifestyle modification weight loss program.     

Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis

BACKGROUND: Small increases in bone mass are commonly seen with existing treatments for osteoporosis, which reduce bone remodelling and primarily prevent bone loss. Since these drugs reduce but do not eliminate risk of fractures, an anabolic agent that would increase bone mass and potentially cure the underlying skeletal problem is needed. METHODS: We did a 3-year randomised controlled trial to find out the effects of 1-34 human parathyroid hormone (hPTH [1-34], 400 U/25 micrograms daily subcutaneously) in postmenopausal women with osteoporosis taking hormone-replacement therapy (n = 17). The controls were women taking hormone-replacement therapy only (n = 17). The primary outcome was bone-mineral density of the lumbar vertebrae, with bone-mineral density at other sites and vertebral fractures as secondary endpoints. FINDINGS: Patients taking hormone-replacement therapy and PTH (1-34) had continuous increase in vertebral bone-mineral density during the 3 years, whereas there was no significant change in the control group. The total increase in vertebral bone-mineral density was 13.0% (p < 0.001); 2.7% at the hip (p = 0.05); and 8.0% in total-body bone mineral (p = 0.002). No loss of bone mass was found at any skeletal site. Increased bone mass was associated with a reduction in the rate of vertebral fractures, which was significant when fractures were taken as a 15% reduction in vertebral height (p = 0.04). During the first 6 months of treatment, serum osteocalcin concentration, which reflects bone formation, increased by more than 55%, whereas excretion of crosslinked n-telopeptide, which reflects bone resorption, increased by only 20%, which suggests some uncoupling of bone formation and resorption. By 6 months, there were similar increases in both markers, which gradually returned towards baseline as the study progressed. Vertebral bone-mineral density increased most during the first year of PTH treatment. INTERPRETATION: We found that PTH has a pronouned anabolic effect on the central skeleton in patients on hormone-replacement therapy. PTH also increases total-body bone mineral, with no detrimental effects at any skeletal site. The increased vertebral mass was associated with a reduced rate of vertebral fracture, despite increased bone turnover. Bone-mass changes may be consistent with a reduction in all osteoporotic fractures. If confirmed in larger studies, these data have important implications for the treatment of postmenopausal osteoporosis.     

Bone mineral recovery after parathyroidectomy in patients with primary and renal hyperparathyroidism

Patients with hyperparathyroidism (HPT) generally display reduced bone mass due to excessive PTH activity. The effect of parathyroidectomy on bone mass changes in different types of HPT, however, is not well understood. Bone mineral density (BMD) was measured in the distal radius, total body, femoral neck, and lumbar spine by dual energy x-ray absorptiometry in four groups of patients with different hyperparathyroid conditions: primary symptomatic HPT (n = 54), primary asymptomatic (mild) HPT (n = 24), HPT associated with hemodialysis (n = 20), and HPT associated with renal transplant (n = 30). Subsets of patients with primary symptomatic HPT (n = 52), HPT associated with hemodialysis (n = 19), and HPT associated with renal transplant (n = 15) underwent parathyroidectomy, and bone density was measured longitudinally for 3 yr. Patients with primary asymptomatic (mild) HPT did not undergo surgery and were followed prospectively. Before surgery, all groups showed a greater reduction of bone mineral density in cortical bone (distal radius) than in predominantly trabecular bone (lumbar spine). In primary symptomatic HPT, the BMD z-score of the distal radius was -1.80 +/- 0.21 (+/-SEM), and the corresponding figures for the total body, femoral neck, and lumbar spine were -0.60 +/- 0.15, -0.54 +/- 0.14, and -0.53 +/- 0.18 compared with those of an age- and sex-matched reference group. In renal HPT BMD z-scores were -2.51 +/- 0.38 (hemodialysis patients) and -2.83 +/- 0.43 (renal transplant patients) for the distal radius and between -0.81 and -1.46 for the other measured sites. After parathyroidectomy, BMD increased by 1-8% at all sites in patients with primary symptomatic HPT and HPT associated with renal transplant. The largest increase in bone mass was observed in patients with HPT associated with hemodialysis, in whom the improvement amounted to 7-23%. In patients with primary HPT and HPT associated with hemodialysis, this increase in bone density resulted in virtual recovery from their preoperative bone loss. The majority of patients with asymptomatic primary HPT disease (n = 21) maintained their bone density during the follow-up period and have not shown evidence of increases in serum calcium or PTH levels, but three patients followed conservatively underwent parathyroidectomy due to progressive deterioration of BMD. We conclude that, regardless of the etiology, a large proportion of HPT patients show reduced bone density. In patients with primary symptomatic HPT and patients with HPT associated with hemodialysis, bone density increases after parathyroidectomy to an extent that largely restores the preoperative bone loss. However, no anabolic effect of parathyroidectomy on bone mass was observed in patients with HPT associated with renal transplant, probably because of their immunosuppressive therapy.     

Anatomic variation of structural properties of periacetabular bone as a function of age. A quantitative computed tomography study

The shape of the acetabulum, the volume of the periacetabular bone, and its density for 125 patients with a wide age range have been quantified using quantitative computed tomography. The goals were to study the relationship between geometric and densitometric properties and provide normative data for finite-element analysis. Significant correlations were found between acetabular diameter and (1) depth, (2) cancellous periacetabular bone density, and (3) periacetabular total bone volume. Only changes in densitometric properties significantly correlated with age. Sphericity of the acetabulum did not increase with age. Variability in bone morphology and density was found for both male and female groups. Surgeons using purely geometric measures to quantify the integrity of acetabular bone should be aware of their limitations when selecting hardware for total hip arthroplasty.