What is the clinical evidence on regenerative medicine in intervertebral disc degeneration?

PURPOSE: This review aims to explore and summarize the current clinical evidence about the use of regenerative medicine such as mesenchymal stem cells or platelet-rich plasma in intervertebral disc regeneration, in order to clarify the state of art of these novel approaches. MATERIALS AND METHODS: We performed a research of the available literature about regenerative medicine strategies aiming to prevent intervertebral disc degeneration. All preclinical trials and in vitro studies were excluded. Only clinical trials were critically analysed. RESULTS: The manuscript selection produced a total of 7 articles concerning the use of regenerative therapies in intervertebral disc degeneration, covering the period between 2010 and 2016. Articles selected were 4 about the injection of mesenchymal stem cells-related results and 3 using platelet-rich plasma. The total population of patients treated with regenerative medicine strategies were 104 patients. CONCLUSIONS: Regenerative medicine, such as the use of mesenchymal stem cells or platelet-rich plasma, in intradiscal disc degeneration has shown preclinical and clinical positive results. Randomized clinical trials studying the potential of MSCs intradiscal injection have not been conducted, and PRP effect has been studied only preliminarily. Additional more powered high-quality studies are needed to really appreciate the long-term safety and efficacy of regenerative medicine approaches in IDD.

Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal.

Our best pharmacologic agents for osteoporosis treatment prevent no more than 40-60% of osteoporotic fractures in patients at highest risk. Thus, there is a need for agents that can further augment bone mass and reduce fracture risk more substantially. To this end, we investigated the utility of parathyroid hormone (PTH) in combination with established hormone-replacement therapy (HRT) in women with osteoporosis. Fifty-two women who had been on HRT for at least 2 years were enrolled in this trial in which 25 were assigned randomly to remain on HRT alone and 27 were assigned to remain on HRT and also receive daily subcutaneous PTH(1-34) 400 U (25 microg) per day for 3 years. Bone mineral density (BMD) measurements at the spine, hip, and total body as well as biochemical determinations of bone turnover and calcium homeostasis were obtained every 6 months. Lateral thoracic and lumbar spine X-rays were obtained at baseline and annually. Subjects also had measurements of bone density and biochemical indices of bone turnover 1 year after discontinuation of PTH, while HRT was continued. In the group receiving HRT alone, bone density and biochemical variables of bone turnover remained stable throughout the 3-year treatment trial and 1-year follow-up. In the PTH + HRT group, biochemical variables of bone formation and resorption peaked at 6 months and subsequently remained elevated until 30 months at which time levels were indistinguishable from baseline. Subjects in the PTH + HRT group increased bone mass by 13.4+/-1.4% in the spine, 4.4+/-1.0% in the total hip, and 3.7+/-1.4% in the total body. Bone density measurements remained stable 1 year after discontinuation of PTH without any significant loss while women continued HRT. Biochemical variables did not change significantly after cessation of PTH through the 1-year follow-up period. PTH + HRT reduced the percent of women who had vertebral fractures from 37.5% to 8.3% (using a 15% height reduction criterion) and from 25% to 0% (using a 20% height reduction criterion) compared with women receiving HRT alone (p < 0.02 for both). We conclude that ongoing HRT maintains almost all of the PTH-induced bone mass increment for 1 year after discontinuation of PTH. Furthermore, PTH in combination with hormone therapy is an effective means of increasing bone mass throughout the skeleton and specifically reducing vertebral fracture occurrence by 75-100%, compared with HRT alone.

Dual X-Ray absorptiometry in pediatric studies: changing scan modes alters bone and body composition measurements.

The use of dual X-ray absorptiometry (DXA) for measurement of bone mineral and body composition in pediatric subjects faces a major technical issue: body size dictates choice of scan mode. However, different scan modes change results in the same subject, thus affecting the accuracy of bone/body composition measurements and especially the capacity to measure changes owing to either growth or intervention. To evaluate the effect of scan mode selections on measurements of bone mineral and body composition, 13 children with weights at the cutoff point between the pediatric large and adult medium scan modes of Lunar DPX or DPXL (Lunar, Madison, WI) with software 3.6 g (35.3 +/- 0.9 kg or 77.7 +/- 2.0 lb) were scanned by both modes. Adult medium mode gave significantly higher results than pediatric large mode for total body fat mass (11.1%), fat% (10.5%), bone mineral content (8.1%), and bone area (1.3%) (p < 0.02). The differences between pediatric large and adult medium modes in fat measurements increased with increasing body mass index ([BMI], kg/m(2)), body surface area ([BSA], m(2)), and trunk size (mm), whereas the differences in bone mineral measurement tended to be greater only with increasing BMI and BSA. None of the differences were correlated to body weight. This study suggests that scan mode selections based on trunk size, BMI, or BSA instead of body weight may improve continuity of bone and body composition measurements by the DXA technique in pediatric subjects.

Comparative assessment of bone mineral measurements using dual X-ray absorptiometry and peripheral quantitative computed tomography.

A measurement of bone mass is the single most important determinant of future fracture. However, controversy exists as to which technique (dual X-ray absorptiometry (DXA) or peripheral quantitative computed tomography (pQCT), and which site of skeletal measurement (axial vs appendicular) provides the best prediction of fracture risk. The aims of this study were: (1) to determine the ability of pQCT to predict bone mass of the lumbar spine, proximal femur, and distal forearm measured using DXA, and (2) to compare the ability of DXA and pQCT to discriminate prevalent fractures in women with established osteoporosis. One hundred and sixty-five women were studied, including 47 with established osteoporosis (vertebral, hip or Colles' fractures) as well as 118 who had bone mass measurements to assess osteoporosis risk. Each subject had bone mass measured by DXA at the lumbar spine and femoral neck, and at the distal radius by both DXA and pQCT. In women with fractures, bone mass, when expressed as a standardized score, was in general lower using DXA compared with the appendicular skeleton measured using pQCT. Bone mass determinations at all sites were significantly correlated with each other. The highest correlation coefficients were observed within the axial skeleton. In women with fractures, the highest odds ratios were observed at skeletal regions measured using DXA. Likewise, the areas under the receiver-operating characteristic (ROC) curves were comparable at all skeletal regions measured using DXA; and were significantly greater than the areas under the ROC curves for pQCT measurements. In summary, the strongest discriminators of prevalent fractures were measurements using DXA. Measurements of bone mass at the appendicular skeleton, using either DXA or pQCT, were poorly associated with axial bone mass. PQCT has the poorer ability to discriminate persons with fractures, and appears to be less sensitive than measurements using DXA.

Fracture history and bone loss in patients with MS.

OBJECTIVES: We have previously shown that MS patients have significantly reduced bone mass and a high prevalence of abnormal vitamin D status. The object of this study was to characterize the frequency of adulthood fractures in MS patients, prospectively determine rates of bone loss in MS, and determine whether vitamin D status is a predictor of bone loss. METHODS: MS patients (36 women, 18 men) were compared with age- and gender-matched healthy controls (35 women, 14 men). Bone mass was performed by dual x-ray absorptiometry at baseline and at 12-month intervals over 2 years. RESULTS: Fractures in the absence of major trauma had occurred in 2% of controls and 22% of MS patients (p < 0.002). Over the 2 years of prospective follow-up, both women and men with MS lost substantially more bone in the femoral neck than did controls (3% and 6% per year in pre- and postmenopausal women with MS versus 0.5% and 0.8% per year in controls; 7.3% per year in men with MS versus 1.6% per year in controls). Bone loss in the spine was also greater in women with MS than in controls (1.6 to 3.5% per year loss in MS patients versus no change in controls). Duration of steroid treatment beyond 5 months and ambulatory status were both predictors of bone loss. Bone loss in the spine occurred faster in MS patients with low (<20 ng/mL) 25-hydroxyvitamin D levels (1.9% per year, p < 0.04), whereas in those with normal 25-hydroxyvitamin D levels, bone loss was insignificant. At the femoral neck, bone loss was substantial in all patients, but was somewhat faster in the group with low levels of 25-hydroxyvitamin D (5.6% per year, p < 0.0001) compared with the group with high levels of 25-hydroxyvitamin D (4.3% per year, p = 0.03). CONCLUSIONS: MS patients have more frequent fractures and lose bone mass more rapidly than do their healthy age- and gender-matched peers, in part related to insufficient vitamin D. Vitamin D repletion in MS patients who are deficient might reduce, to some extent, the rate of bone loss and decrease osteoporosis-related fractures.

Tumors of the spine. Indications for surgical treatment.

The authors analyze problems inherent to the treatment of spine tumors (in particular surgical indications) especially with regard to metastases. The purpose of treatment must be that of improving the quality of life and, perhaps, prognosis. In this sense it is hoped that when indications exist surgical treatment will be as timely and radical as possible.

Dual-energy X-ray absorptiometry: fat estimation errors due to variation in soft tissue hydration.

Dual-energy X-ray absorptiometry (DXA) is rapidly gaining acceptance as a reference method for analyzing body composition. An important and unresolved concern is whether and to what extent variation in soft tissue hydration causes errors in DXA fat estimates. The present study aim was to develop and validate a DXA physical hydration model and then to apply this model by simulating errors arising from hypothetical overhydration states. The DXA physical hydration model was developed by first linking biological substance elemental content with photon attenuation. The validated physical model was next extended to describe photon attenuation changes anticipated when predefined amounts of two known composition components are mixed, as would occur when overhydration develops. Two overhydration models were developed in the last phase of study, formulated on validated physical models, and error was simulated for fluid surfeit states. Results indicate that systematic errors in DXA percent fat arise with added fluids when fractional masses are varied as a percentage of combined fluid + soft tissue mass. Three independent determinants of error magnitude were established: elemental content of overhydration fluid, fraction of combined fluid + soft tissue as overhydration fluid, and initial soft tissue composition. Small but systematic and predictable errors in DXA soft tissue composition analysis thus can arise with fluid balance changes.

Reduced bone mass and fat-free mass in women with multiple sclerosis: effects of ambulatory status and glucocorticoid Use.

Multiple sclerosis (MS) is associated with reduced bone mass and vitamin D deficiency. The underlying pathophysiology of the bone disease is uncertain, however, acute and long-term glucocorticoid use, progressive immobilization, vitamin D deficiency, and possibly skeletal muscle atrophy are likely to be determinants. The aims of this study were to determine (a) whether multiple sclerosis is associated with reduced fat-free mass and (b) whether in patients with multiple sclerosis, ambulation ability or glucocorticoid use is associated with bone mass and/or fat-free mass. Seventy-one female patients with MS were compared with 71 healthy, age-matched female controls. Total body bone mineral content (TBBMC, kg), fat mass (FM, kg), and fat-free mass (FFM, kg) were measured using dual X-ray absorptiometry. Disability status was graded according to the Kurtzke Expanded Disability Status Scale (EDSS) as ambulatory, with or without aide (EDSS score of 0 to 6.5), or predominantly wheelchair bound (EDSS score > 6.5). The patients with MS, when compared to age-comparable controls, had deficits in TBBMC ( approximately 8%, -0.3 +/- 0.1 SD, P < 0.04) and FFM ( approximately 5%, -0.3 +/- 0.1 SD, P < 0.01). Both TBBMC and FFM were negatively associated with EDSS score (r = 0.33, P < 0.01, and r = 0.41, P < 0.01, respectively). Patients with MS who were nonambulatory had even greater deficits in TBBMC and FFM as compared with age-matched controls (-0.6 +/- 0.1 SD, P < 0.01, and -0.6 +/- 0. 1 SD, P < 0.01, respectively). By contrast, as compared with age-comparable controls, ambulatory patients with MS had no deficits in bone mass or soft tissue mass. When compared with ambulatory patients with MS, nonambulatory patients with MS had deficits in TBBMC and FFM (P < 0.01 and P < 0.01, respectively). The difference in TBBMC was largely caused by the difference in fat-free mass, whereas the difference in FFM was largely caused by the difference in glucocorticoid use based on analysis of covariance. We conclude that in patients with multiple sclerosis, physical disuse is the main determinant for the reduction in bone mass. Glucocorticoid treatment is the major determinant of the reduction in fat-free mass and thus also contributes to the reduction in bone mass.

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.

Dual-energy X-ray absorptiometry body composition model: review of physical concepts.

Although dual-energy X-ray absorptiometry (DXA) is widely used in clinical research as a means of quantifying body composition, there remains at present little published information that reviews the method's underlying physical basis. Because a clear understanding of DXA physical concepts is integral to appropriate use and interpretation, we present here a three-section review that includes both relevant in vitro and in vivo experimental demonstrations. In the first section we describe the main physical principles on which DXA is based. The section that follows presents a step-by-step analysis of the DXA two-component soft tissue model. In the final section we demonstrate how knowledge of physical concepts can lead to resolution of important methodological concerns, such as the influence of hydration changes on DXA fat estimates. A thorough understanding of DXA physical concepts provides a basis for appropriate interpretation of measurement results and stimulates many new and important research questions.

Do genetic factors explain associations between muscle strength, lean mass, and bone density? A twin study.

Are the associations between muscle strength, lean mass, and bone mineral density (BMD) genetically determined? Based on within-pair differences in 56 monozygotic (MZ) and 56 dizygotic (DZ) female twin pairs, mean age 45 yr (range 24-67), BMD was associated with lean mass, independent of fat mass and height (P < 0.05). A 10% increment in femoral neck (FN) BMD was associated with a 15% increment in lean mass (approximately 6 kg). BMD was associated with muscle strength (measured in 35 pairs) before, but not after, adjusting for lean mass. Based on age-adjusted cross-sectional analyses, same-trait correlations (+/- SE) in MZ pairs were double those in DZ pairs: FN BMD (0.62 +/- 0.08, 0.33 +/- 0.12) and lean mass (0.87 +/- 0.03, 0.30 +/- 0.11; all P < 0.001), consistent with a genetic hypothesis. The cross-trait correlation (r) between lean mass and FN BMD in the same individual was 0.43 +/- 0.06. The cross-trait cross-twin correlation between lean mass in one twin and FN BMD in the other was 0.31 +/- 0.07 in MZ pairs, approximately 75% of the cross-trait correlation (r) and 0.19 +/- 0.09 in DZ paris (P < 0.001). After adjusting for height and fat mass, the MZ and DZ cross-trait cross-twin correlations were no different (0.16 +/- 0.08 and 0.13 +/- 0.09, respectively). Therefore, genetic factors account for 60-80% of the individual variances of both FN BMD and lean mass, and > 50% of their covariance. The association between greater muscle mass and greater BMD is likely to be determined by genes regulating size.

Effects of insulin on body composition in patients with insulin-dependent and non-insulin-dependent diabetes.

Insulin is used to control blood glucose but may have an adverse effect on the amount and distribution of fat mass and other cardiovascular risk factors. To test this hypothesis the effect of insulin therapy on blood glucose, body composition, and lipid levels was measured during 6 months in 9 patients with newly diagnosed insulin-dependent (Type 1) diabetes mellitus (IDDM) and 15 patients with non-insulin dependent (Type 2) diabetes (NIDDM) and secondary failure of therapy with oral hypoglycaemic agents. Both groups received similar daily doses of insulin (approximately 0.6 units kg-1 day-1). Glycaemic control improved during 6 months treatment in both groups, although the reduction in HbA1c was greater in IDDM (5.2 +/- 0.7%) than in NIDDM (2.0 +/- 0.4%, p < 0.001). All parameters of the lipid profile improved in IDDM but not in NIDDM. Body weight, lean mass, and fat mass, measured by dual energy x-ray absorptiometry, increased at 1 month in IDDM but not in NIDDM. By 6 months, body weight had increased more in IDDM than NIDDM (9.1 +/- 1.2 vs 3.77 +/- 0.5 kg, p < 0.01). The increase in weight was predominantly lean mass in IDDM (60.4 +/- 9.3%) and fat mass in NIDDM (59.9 +/- 8.4%). The increase in lean mass was greater in IDDM than NIDDM (5.6 +/- 1.1 vs 1.4 +/- 0.3 kg, p < 0.001). Fat mass increased by similar increments in IDDM and NIDDM (3.4 +/- 0.8 vs 2.4 +/- 0.5 kg, p = ns) and was predominantly an increase in trunk fat (IDDM: 2.3 +/- 0.6 kg, NIDDM: 2.0 +/- 0.4 kg, p = ns). The central/peripheral fat mass ratio prior to treatment was lower in IDDM than NIDDM (0.64 +/- 0.05 vs 1.09 +/- 0.09, p < 0.01) and then increased in IDDM by 0.32 +/- 0.15 (p = 0.07) and in NIDDM by 0.22 +/- 0.06 (p < 0.001). In conclusion, insulin therapy is associated with weight gain in both IDDM and NIDDM. In the former, weight gain reflects increases in lean mass whereas in NIDDM it reflects an increase in trunk fat mass. It remains to be determined whether this trend to central obesity partly offsets other benefits of insulin therapy in NIDDM.

Does weight-bearing exercise protect against the effects of exercise-induced oligomenorrhea on bone density?

Does weight-bearing exercise offset bone loss associated with oligomenorrhea? If so, bone mineral density (BMD) will be stable at weight bearing sites but decrease at non-weight-bearing sites with increasing duration of oligomenorrhea. To test this hypothesis, BMD (g/cm2), was measured by dual-energy X-ray absorptiometry in 41 oligomenorrheic ballet dancers aged 17.7 +/- 0.2 years (mean +/- SEM) and 46 age-matched controls with normal menstrual function. BMD correlated negatively with the duration of oligomenorrhea at weight-bearing and non-weight-bearing sites (femoral neck, r = -0.33, p < 0.05; Ward's triangle, r = -0.29, p = 0.06; trochanter, r = -0.33, p < 0.05; lumber spine, r = -0.25, p = 0.1; skull, r = -0.29, p = 0.06; arms, r = -0.32, p < 0.05; ribs, r = -0.30, p = 0.06). The slopes of the regression of BMD on duration of oligomenorrhea were greater at the proximal femur (trochanter, -0.28 +/- 0.13, femoral neck, -0.24 +/- 0.11; Ward's triangle, -0.29 +/- 0.15) than the skull (-0.15 +/- 0.08, p < 0.05, p < 0.1, p < 0.1 respectively). The slopes at the trochanter and femoral neck were also greater than at the ribs (-0.10 +/- 0.05; both p < 0.1). In the dancers with oligomenorrhea of less than 40 months duration, BMD was higher than the age-predicted mean at weight-bearing sites (except the lumber spine), but not at non-weight-bearing sites (femoral neck, 9.1 +/- 3.4%; Ward's triangle, 10.0 +/- 1.7%; trochanter, 9.4 +/- 4.1%, all p < 0.05; lumbar spine, -2.1 +/- 2.7%, NS; skull, -2.5 +/- 2.1%, NS; ribs, -3.0 +/- 1.6% NS; arms, -3.9 +/- 1.6%; p < 0.05). In the dancers with greater than 40 months oligomenorrhea, BMD was no higher than the age predicted mean, at the weight bearing sites, and was lower at non-weight bearing sites (femoral neck, 4.3 +/- 2.3%, NS; Ward's triangle, 3.5 +/- 3.2%, NS; trochanter, 2.1 +/- 2.7%, NS; lumbar spine, -3.8 +/- 2.1%, NS; arms, -7.5 +/- 0.8%, p < 0.05; skull, -6.2 +/- 1.8%, p < 0.01; ribs, -5.4 +/- 1.1%, p < 0.0001). In conclusion, weight-bearing exercise is unlikely to offset the deleterious effects of oligomenorrhea. Bone loss appears to occur at all sites but may begin from a higher level at weight-bearing sites and may proceed more rapidly.

Equivalent deficits in bone mass of the vertebral body and posterior processes in women with vertebral fractures: implications regarding the pathogenesis of spinal osteoporosis.

Reduced bone mass of the spine in women with vertebral fractures is attributed to excessive trabecular bone loss from the vertebral body. However, the measurement obtained by posteroanterior (PA) scanning includes the posterior processes and the vertebral body, each comprising about 50% of the total vertebral mass. Thus, the deficit in bone mass by PA scanning may be due to deficits in one or both of these structures. We asked two questions: (1) In healthy women, is the age-related diminution in bone mass of the vertebral body greater than the diminution at the posterior processes? (2) In women with vertebral fractures, is the deficit in bone mass at the vertebral body, the fracture site in spinal osteoporosis, greater than at the posterior processes? Bone mass of the posterior processes and vertebral body of the third lumbar vertebra was measured by lateral scanning using dual-energy X-ray absorptiometry (DXA). Compared with 27 premenopausal women, deficits in 27 postmenopausal women at the posterior processes and vertebral body, respectively, were 35.9 +/- 3.7 and 25.2 +/- 4.1% (p < 0.05); t score, -1.5 +/- 0.2 and -1.1 +/- SD (p = 0.09). Compared with the postmenopausal (age-matched) women, deficits in 21 women with vertebral fractures at the posterior processes and vertebral body, respectively, were 22.6 +/- 4.9 and 24.5 +/- 8.3% (p = NS); Z score, -0.8 +/- 0.2 and -0.8 +/- 0.3 (p = NS). In vivo the bone mass of the vertebral body as a percentage of the whole vertebra was 45.7 +/- 0.1 in premenopausal women, 48.9 +/ 1.9 in postmenopausal women, 51.5 +/- 1.1 in women with low bone mass but no fractures, 52.7 +/- 2.4 in women with vertebral fractures, and 51.9 +/- 2.5% in vitro, based on autopsy specimens from 19 postmenopausal women aged 65 - 95 years. The lower spinal bone density measured using PA scanning in women with spine fractures may not be due to excessive or disproportionate trabecular bone loss from the vertebral body because comparable deficits are found at the posterior processes. Whether these deficits are due to reduced peak bone mass, trabecular bone loss, cortical bone loss, or varying combinations of these mechanisms remains to be established.

Inhomogeneity in body fat distribution may result in inaccuracy in the measurement of vertebral bone mass.

When bone mineral content (BMC) is measured by dual X-ray absorptiometry (DXA), the X-ray beam is attenuated by bone and soft tissue. Since the component of the attenuation caused by the soft tissue overlying bone cannot be measured, the attenuation caused by soft tissue adjacent to bone is measured and is used in the calculation of BMC. the assumption underlying this approach is that the amount and composition of this adjacent soft tissue is the same as overlying bone. The aim of this study was to examine the validity of this assumption by determining whether fat distribution over and adjacent to bone differ and whether this introduces accuracy errors in the measurement of BMC by postero-anterior (PA) and lateral scanning. BMC (posterior processes plus vertebral body, g) of the third lumbar vertebra was 17.3 +/- 0.7 by PA and 17. +/- 0.7 by lateral scanning in 27 premenopausal women (p = NS), but 2.7 g or 20% higher by PA than scanning in 27 postmenopausal women (14.4 +/- 0.7, 11.7 +/- 0.5, p<0.01). Thus, the respective diminutions across age by PA scanning was about half that by lateral scanning (16.8 +/- 3.9%, 31.2 +/- 3.0%, p<0.01). Percent fat in the soft tissue baseline (anterior to bone, ST-ant) used to derive BMC by lateral scanning by 2.6 +/- 0.7% in premenopausal women and 7.5 +/- 1.0% in postmenopausal women (both p<0.01). After adjusting for these differences in percent fat, BMC by PA and lateral scanning no longer differed.

Reduced femoral neck bone density in the daughters of women with hip fractures: the role of low peak bone density in the pathogenesis of osteoporosis.

Low bone density in women with hip fractures ("senile" osteoporosis) may be due to excessive bone loss or low peak bone density. If excessive bone loss is responsible, then no reduction in bone density is expected in their daughters. If low peak bone density is responsible, then bone density should also be reduced in their daughters because genetic and family environmental factors influence the variability in bone density. Bone density was measured using dual-photon absorptiometry and expressed as a standardized deviation or Z score relative to 697 controls, adjusting for age, height, weight, and menopausal status. In 74 women with hip fractures, the Z score (mean +/- SEM) was -0.52 +/- 0.14 (P < 0.001) at the femoral neck, -1.04 +/- 0.17 (P < 0.001) at the femoral shaft, and -0.43 +/- 0.10 (P < 0.001) at the lumbar spine. In their 41 daughters, the Z score was -0.40 +/- 0.17 (P < 0.05) at the femoral neck, -0.41 +/- 0.19 (P < 0.001) at the femoral shaft, and 0.23 +/- 0.13 (NS) at the lumbar spine. We conclude that daughters of women with hip fractures are likely to be at increased risk for hip fractures themselves because they have reduced femoral neck bone density. Femoral neck fractures may not be entirely attributable to trauma; reduced bone density is likely to contribute and may be caused by the attainment of a lower peak femoral neck bone density.

Bone density at weight-bearing and nonweight-bearing sites in ballet dancers: the effects of exercise, hypogonadism, and body weight.

Exercise is recommended as a means of preventing osteoporosis. When intensive, weight-bearing exercise is often associated with hypogonadism. As weight-bearing exercise is likely to be more beneficial at weight-bearing than nonweight-bearing sites, and hypogonadism is likely to be more detrimental to trabecular than cortical bone, we tested the hypothesis that exercise and hypogonadism result in differing regional effects: net benefits at weight-bearing, predominantly cortical sites, and net deficits at nonweight-bearing trabecular-rich sites. Bone density (grams per cm2), body fat, and fat-free mass (kilograms) were measured using dual x-ray absorptiometry in 44 ballet dancers, aged 17.0 +/- 0.2 yr (mean +/- SEM), 18 sedentary amenorrheic girls with anorexia nervosa, and 23 girls of comparable age with regular menstrual cycles. Bone density, expressed as a percentage above or below the mean in the girls with regular menstrual cycles, was normal or elevated at weight-bearing sites in dancers [femoral neck, 3.1 +/- 1.7% (P = NS); Wards triangle, 4.1 +/- 2.3% (P = NS); trochanter, 5.9 +/- 1.9% (P < 0.05)] and normal or reduced at these sites in girls with anorexia nervosa [-10.5 +/- 3.8% (P < 0.05), -7.8 +/- 4.3% (P = NS), and -8.7 +/- 4.0% (P < 0.05), respectively]. By contrast, deficits similar to those in girls with anorexia nervosa were found in dancers at nonweight-bearing sites [ribs, -5.7 +/- 0.8% (P < 0.01); arms, -4.6 +/- 1.1% (P < 0.01); skull, -5.9 +/- 1.3% (P < 0.01)] before, but not after, correcting for fat mass. Fat mass was 7.8 +/- 0.4 kg in dancers, similar to that in girls with anorexia nervosa (6.3 +/- 0.7 kg) and lower than that in girls with regular menstrual cycles (16.8 +/- 1.6 kg; P < 0.01). The net result of vigorous exercise, hypogonadism, and leanness in athletic amenorrhea may not be generalized osteoporosis. Weight-bearing exercise may offset the effects of hypogonadism at predominantly cortical weight-bearing sites, such as the proximal femur. Non-weight-bearing sites and weight-bearing sites containing substantial amounts of trabecular bone, such as the lumbar spine, may be adversely affected by hypogonadism while benefiting little from weight-bearing exercise. Deficits at nonweight-bearing sites may be attenuated by maintenance of body weight.

Metastatic bone tumors. Nonsurgical treatment. Outcome and survival.

Of 683 (16.1%) consecutive patients investigated from October 1984 to December 1985, 110 had various malignant tumors and secondary bone involvement. In 82 of 110 patients (74.5%), the primary tumor was located in the breast, and the percentage of clinical and radiographic objective responses (OR) of their bone lesions (42.7% and 22.8%, respectively) was higher than for cancer in other sites (clinical OR, 21.4%; radiographic OR, 15.8%). The average survival time of 82 breast cancer patients was 87.4 months, or 38 months from the diagnosis of the bone metastases. Of the 110 patients with bone metastases, 60 patients (54.5%) had secondary spinal involvement. The clinical and radiographic OR (38.4% and 30.2%) were better in the patients with vertebral metastases than in the patients with bone metastases in other sites (clinical OR, 36%; radiographic OR, 9.1%). The average survival time of the patients with vertebral involvement was 99.4 months, or 40.4 months from the time of diagnosis of the bone metastases. From the results obtained, in terms of OR and survival for patients with bone metastases, early and aggressive treatment should be considered to improve the patients' life quality.

Body composition following hemodialysis: studies using dual-energy X-ray absorptiometry and bioelectrical impedance analysis.

The detection, prevention and treatment of disease is greatly facilitated by the availability of accurate and non-invasive techniques for measuring the amount and regional distribution of fat mass and fat-free mass. As differing degrees of hydration may influence these measurements, we used dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) to detect changes in hydration following hemodialysis, and to determine whether fat mass, fat-free mass and bone density measurements were affected by these fluid changes. Ten subjects (7 men, 3 women) mean age 46.2 years (range 25-68 years), with renal failure had bone density, fat-free mass and fat mass measured by DXA, and total body water and fat-free mass measured by BIA, before and after hemodialysis. Thirty-two subjects had fat-free mass measured by DXA and BIA in an attempt to derive new equations (using fat-free mass measured by DXA as the reference standard) to improve the predictive value of BIA. The new equations were then used to derive the changes in fat-free mass following hemodialysis measured using BIA. In absolute terms, total tissue measured by DXA (r = 0.99, p = 0.01) and total body water measured by BIA (r = 0.91, p = 0.01) correlated with gravimetric weight. Following hemodialysis, fat mass and bone density measured by DXA were unaffected by the fluid changes. The change in gravimetric weight was 1.8 +/- 0.3 kg, p = 0.01 (mean +/- SEM). This change was measured as 1.9 +/- 0.3 kg by DXA, -0.9 +/- 1.0 kg by BIA using the published equation for fat-free mass, and 3.2 +/- 0.4 kg using the new equation for fat-free mass.(ABSTRACT TRUNCATED AT 250 WORDS)