A systematic review of the effect of alendronate on bone mineral density in men.

Alendronate is known to increase bone mineral density (BMD) at the lumbar spine and hip in women, but less information is available in men. We conducted a systematic review of randomized controlled trials to determine whether oral alendronate improves BMD at the lumbar spine and hip in men with low bone mass or prevalent fractures, compared with men treated with placebo, calcium, or vitamin D. In three trials in men, BMD (measured by dual-energy X-ray absorptiometry) increased at 2-3 yr (compared to baseline) at the lumbar spine and femoral neck in alendronate-treated patients compared to controls. The pooled estimates of changes in BMD with 10 mg of alendronate daily compared to controls were as follows: 7.8% over 2-3 yr (95% confidence interval [CI] = 4.8- 10.8) at the lumbar spine and 3.8% (95% CI = 2.3-5.3) at the femoral neck (p < 0.001 for treatment effect in each analysis). Statistically significant heterogeneity of treatment effect was noted between trials. We conclude that 10 mg of oral daily alendronate is significantly associated with increase in BMD at the lumbar spine and hip in men over 2-3 yr and that these changes are similar to those previously observed in postmenopausal women.     

Bone Mineral Density in Patients with Human Immunodeficiency Virus Infection

The Object of this study was to determine whether HIV infection is associated with decreased bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry at total body, lumbar spine, and hip in 45 men with HIV infection and compared with sex, age, and weight-matched controls. Repeat scans were performed after a mean interval of 15 months in 21 patients to determine whether there were detectable losses of BMD. Compared with controls, the HIV patients had marginally lower BMD at the lumbar spine (P= 0.04) but there was no significant difference in total body or hip BMD. None of the patients had reduced BMD to levels associated with a diagnosis of osteoporosis. On longitudinal follow-up, a small decrease in total body BMD (−1.6%; P= 0.02) was observed but there was no significant change in spine and hip BMD. In spite of the many features of HIV infection that might be expected to cause a reduction in BMD such as cytokine activation, decreased physical activity, small bowel disease, hypogonadism, and direct infection of osteogenic cells by HIV, we found only minimal differences in BMD between HIV patients and controls. Furthermore, the HIV patients studied did not appear to show excessive loss in bone mineral over time. Received: 12 November 1996 / Accepted: 5 March 1997     

Altered bone mineral metabolism in patients with osteoarthritis

OBJECTIVE: Investigation of the relationship between osteoarthritis (OA) and mineral density, and determination of any alteration in bone mineral, metabolism as assessed by biochemical markers of bone resorption and formation. METHODS: Forty females and 20 males were included in the study. Spinal OA as well as knee OA were defined from radiographs and graded according to Lane et al.'s and Spector et al.'s scoring systems. Bone mineral density (BMD) of the lumbar spine was measured by osteo CT. Bone turnover rates were estimated by measuring biochemical markers of bone resorption (urinary deoxypyridinoline) and bone formation (bone-specific alkaline phosphatase). Forty females and 20 males of the same age were studied as a control group. RESULTS: BMD was greater in women with spinal OA as compared to controls (P < 0.05). Also, males with OA had a non-significantly higher BMD than controls. The bone resorption markers were higher than normal values. However, they were lower than the control group. Similarly, the bone formation markers were lower as compared to the control group. CONCLUSION: Spinal OA is associated with higher BMD. This protective effect of spinal OA against osteoporosis may be mediated through decreased rate of bone turnover.     

The relationship between regional bone turnover measured using 18F-fluoride positron emission tomography and changes in BMD is equivalent to that seen for biochemical markers of bone turnover.

Bone turnover is an important determinant of fracture risk. (18)F-fluoride positron emission tomography ((18)F-PET) allows the direct assessment of bone turnover at the clinically important skeletal sites such as the lumbar spine. The aim of this study was to determine if the relationship between regional bone turnover measured using (18)F-PET and changes in bone mineral density (BMD) is equivalent to that seen for global skeletal measurements of biochemical markers of bone turnover. Forty-three women who had previously had an (18)F-PET scan at the lumbar spine, assessment of biochemical markers of bone turnover, and a dual-energy X-ray absorptiometry scan of BMD at the lumbar spine and hip (baseline assessments) were split into 1 of 2 groups: (1) 22 women who commenced treatment for osteoporosis within 2mo of having the baseline assessments (Treatment group); (2) 21 women who had not taken any treatments for osteoporosis since having the baseline assessments (Untreated group). Sixteen of the women in the Treatment group started risedronate therapy as part of a prospective study they were participating in, whereas the decision to treat the remaining 6 women was made by the subject's treating physician. Subjects had between 2 and 5 BMD scans over a median follow-up time of 4.1yr to estimate the annual percentage change in BMD since baseline. The relationship between the tertiles of (18)F-PET skeletal kinetic parameter K(i), reflecting regional bone turnover, and annual changes in lumbar spine and hip BMD were compared to that seen for bone formation (bone-specific alkaline phosphatase, BSALP) and bone resorption (urinary deoxypyridinoline) markers. Treated women in the highest tertile of both regional ((18)F-PET) and global (biochemical markers) bone turnover showed the greatest annual percentage increases in lumbar spine BMD. The annual increase in lumbar spine BMD was 1.8%, 2.2%, and 3.2% for women in the lowest, middle, and highest tertile of BSALP, respectively, which was similar to that obtained for the regional measurement of K(i) of 1.7%, 2.2%, and 2.7% respectively. Untreated women in the highest tertile of regional and global bone turnover had larger decreases in lumbar spine BMD compared to those women in the lowest tertile, with a 1.4- to 4.8-fold difference in the annual decrease in BMD between the two. Less consistent patterns were observed when assessing the relationship between regional and global bone turnover with changes in hip BMD. This study has demonstrated that the relationship between regional bone turnover measured directly at the lumbar spine with changes in BMD is similar to that seen for global skeletal bone turnover using biochemical markers.     

Prevalence of low bone mineral density in a low‐income inner‐city population

Bone mineral density (BMD) is an important factor linked to bone health. Little is known of the prevalence of low BMD and its associated risk factors in an urban underserved population. Between 2001 and 2004, we recruited 338 subjects who completed drug use and medical history questionnaires, underwent hormonal measurements, and underwent whole‐body dual‐energy X‐ray absorptiometry (DXA) for evaluation of BMD and body composition. Of these, 132 subjects had site‐specific DXA (lumbar spine and hip) performed. Osteoporosis was defined as a T‐score of –2.5 or less for men 50 years of age and older and postmenopausal women and a Z‐score of –2.0 or less in men younger than 50 years of age and premenopausal women at either the lumbar spine, total hip, or femoral neck, according to National Osteoporosis Foundation (NOF) guidelines. The cohort consisted of mostly African‐American, middle‐aged people with a high prevalence of illicit drug use, 50% HIV⁺, and 39% hepatitis C⁺. Osteoporosis was identified in 22% of subjects (24 men, 5 women), with the majority of cases (90%) attributable to osteoporosis at the lumbar spine. Osteoporosis was more common in men than in women. Lower whole‐body BMD among women was associated with multiple risk factors, but only with lower lean mass among men. Osteoporosis was highly prevalent in men, mainly at the spine. The risk factors for bone loss in this population need to be further clarified. Screening men for osteoporosis starting at age 50 might be warranted in this population given the multiple risk factors and the unexpectedly high prevalence of low BMD. © 2011 American Society for Bone and Mineral Research.     

Ghrelin and bone: is there an association in older adults?: the Rancho Bernardo study.

Laboratory studies suggest that ghrelin is involved in bone metabolism, but studies of ghrelin and bone in humans are limited. We studied sex-specific associations of ghrelin with BMD, NTX, and bone loss. Ghrelin was not associated with BMD or bone loss in either sex. There was a significant inverse association with NTX in men but not in women. INTRODUCTION: Ghrelin is a gastric hormone recently shown to be associated with bone metabolism in animal and in vitro studies. Studies in humans are limited. We investigated the association of ghrelin with BMD, the bone resorption marker N-telopeptide (NTX), and bone loss in older men and women. MATERIALS AND METHODS: Participants were 977 community-dwelling men and non-estrogen-using postmenopausal women, 50-91 years of age. Plasma ghrelin was measured by radioimmunoassay from blood obtained between 1984 and 1987. Between 1988 and 1991, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA. Axial BMD measurements were repeated an average of 4 years later in 544 participants. Bone turnover was assessed by NTX in urine obtained at the same time as the initial BMD. Multiple regression analyses were used to test sex-specific associations of ghrelin with BMD, NTX, and bone loss in both sexes. RESULTS: No significant ghrelin-BMD or ghrelin-bone loss associations were observed in either sex, after adjusting for age and body mass index (BMI). Ghrelin was inversely associated with NTX in men and positively associated with NTX in women, independent of age. After adjusting for both age and BMI, this association reached statistical significance in men and was weakened in women. CONCLUSIONS: Ghrelin may be associated with bone turnover, but there is no evidence for an association with BMD or short-term change in BMD in older adults.     

Body composition and bone mineral density of Chinese women with vertebral fracture

This study was designed to compare the body composition and bone mineral density measurements (BMD) in Chinese women with vertebral fracture and normal controls. A total of 400 community dwelling Chinese women aged 70–79 years old were studied. Vertebral height ratios were calculated from lateral thoracic and lumbar spine X-rays and subjects were classified into definite cases (n = 122), doubtful cases (n = 138) and normal controls (n = 140). Bone mineral density and body composition measurements were made by dual X-ray densitometry. The height, fat mass, lean mass, and BMD at all sites were significantly lower in patients with definite fracture than normal controls. Nevertheless, BMD at the hip was more predictive of vertebral fracture than BMD at the spine, the odds ratio in the lowest quartile of hip BMD being 3.8 (95% C.I. = 1.3 to 10.9). Finally, the extent of spinal deformity was poorly predicted by a combination of the anthropometric and BMD measurements, as only 12% of the total variance in TD1 was accounted for.     

BMD is reduced in HIV-infected men irrespective of treatment.

Osteoporosis has be reported to be a complication of active antiretroviral therapy of HIV infection. We studied 148 HIV-infected men stratified according to their treatment. Our data show that these patients have an average 9% decreased BMD, irrespective of their treatment. Low body mass index and high resorption markers were associated with low bone density. INTRODUCTION: Osteoporosis has been reported in HIV-infected (HIV+) patients, and it has been suggested that it may be linked to protease-inhibitor treatments (PI). MATERIALS AND METHODS: To assess this risk and to investigate its putative link with treatments, we compared the bone density of HIV+ men, who were either receiving treatment (including PI [PI+], n = 49; without PI [PI-], n = 51) or untreated (UT, n = 48). We included 81 age-matched control HIV-negative (HIV-) males (age, 40 +/- 8 years). RESULTS: BMD adjusted for age (Z-score) was lower in the HIV+ patients at the lumbar spine (HIV+: -1.08 +/- 1.21, HIV-: -0.06 +/- 1.26, p < 0.001) and the femoral neck (HIV+: -0.39 +/- 1.05, HIV-: 0.25 +/- 0.87, p < 0.001). The prevalence of osteoporosis was 16% in HIV+ and 4% in HIV- subjects (p < 0.01). In the HIV+ subjects, the Z-score was correlated only to body mass index (r = 0.27 at lumbar spine and 0.35 at femoral neck). Untreated HIV+ patients had a negative Z-score (-0.82 +/- 1.15 for the lumbar spine), which was not different from the one of treated HIV+ patients. In the PI+ and PI- groups, the Z-score did not depend on the presence of lipodystrophy or the proportion of fat in the abdomen and legs measured by DXA. Markers of bone remodeling were measured in the 132 HIV+ and 35 HIV- subjects. Compared with controls, HIV+ patients had lower bone alkaline phosphatase and higher urinary cross-laps/Cr, which was negatively correlated with the Z-score at both the femoral neck (r = -0.22) and lumbar spine (r = -0.21). TNFalpha was increased in untreated compared with treated HIV+ subjects and was not correlated to the Z-score. CONCLUSION: Our cross-sectional study does not show any deleterious effect of the treatment but does indicate a decrease in bone density in HIV+ patients irrespective of the treatment. This low bone density is in part related to the low body weight and is associated with increased bone resorption.     

Cross-sectional assessment of age-related bone loss in men: the MINOS study

There are few data on osteoporosis in men, but cross-sectional studies have shown that age-related bone loss in men is of lower magnitude than in women. To elucidate some controversies related partially to methodological aspects, we measured bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) at various skeletal sites (spine, hip, and whole body using a Hologic QDR-1500 device; forearm using an Osteometer DTX 100 device) in a large cohort of 1040 men, aged 19-85 years. The final investigation was performed on 934 men, aged 19-85 years, after exclusion of 106 men with disease or treatment known to affect bone metabolism. Peak BMD was achieved at 25 and 29 years at the lumbar spine and hip, respectively, but only at 40 and 37 years at the distal forearm and whole body, respectively. The magnitude of bone loss between peak bone mass and 80 years of age was linear at most sites and averaged 13%-18%; that is, SD of 1.1-1.8 from peak BMD, except for Ward's triangle, which showed a marked bone loss of 43% (i.e., 2.5 SD), and for the lumbar spine. In the entire cohort, increase of the average lumbar spine BMD after the age of 55 years was related to the development of osteoarthritis, because, in men without severe arthritis, lumbar spine BMD continued to decrease. Height-adjusted partial correlations indicate that both the mineral content and the area of long bones of the limbs increased with age up to 50 years, followed by a significant decrease of BMD without change of bone surface. SD of mean BMD increased significantly with age at most skeletal sites. In summary, age-related change of BMD varied according to skeletal site in men with peak bone mass achieved earlier at sites rich in trabecular bone than at those rich in cortical bone. Bone loss varied according to skeletal site from 14% to 43%. The variability of BMD increased with age, which may reflect interindividual variability of age-related bone loss.     

Osteopenia in patients infected by the human immunodeficiency virus. A case control study

Summary - In the last few years, the use of highly active antiretroviral therapy has radically modified the prognosis of human immunodeficiency virus (HIV) infection. Osteonecrosis and osteoporosis are among the bone complications recently described in HIV-infected patients. We report a preliminary study comparing 47 HIV-infected patients (31 men and 16 women) to 47 age- and sex-matched controls. Bone mineral density was lower in patients than in controls: in men, 0.919 +/- 0.120 g/cm2 vs. 1.010 +/- 0.139 g/cm2 (P = 0.01) at the total hip and 0.948 +/- 0.100 g/cm2 vs. 1.043 +/- 0.117 g/cm2 (P = 0.0008) at the lumbar spine; in women, 0.912 +/- 0.149 g/cm2 vs. 0.968 +/- 0.090 g/cm2 at the total hip (P = 0.17) and 0.989 +/- 0.152 g/cm2 vs. 1.080 +/- 0.097 g/cm2 (P = 0.01) at the lumbar spine. HIV-infected males were more likely to have osteopenia and osteoporosis, as compared to the male controls (19 vs. 14 and 4 vs. 1, respectively, P = 0.02). None of the women had osteoporosis; nine HIV-infected women and one female control had osteopenia (P = 0.003). No fractures were recorded. In this preliminary study, no evidence supporting a relationship between bone loss and protease inhibitor treatment was found.     

Leptin predicts BMD and bone resorption in older women but not older men: the Rancho Bernardo study.

We studied the relation of leptin to bone, bone loss, and bone turnover in community-dwelling men and women. Leptin predicted higher BMD and lower bone turnover only in women. Leptin was not associated with 4-year bone loss in either sex. INTRODUCTION: Leptin, the protein product of the obesity (OB) gene produced in fat tissue, was originally thought to be involved only in the regulation of food intake and energy balance. Recent evidence suggests that leptin may play a role in the pathophysiology of several chronic diseases. Studies of the association between leptin and bone have been numerous yet inconclusive. Only one previous longitudinal study has been reported, which showed no association of leptin with BMD after adjusting for body size. MATERIALS AND METHODS: We report the association of serum leptin with BMD at the hip, spine, and midshaft radius in community-dwelling men (n = 498) and nonestrogen-using postmenopausal women (n = 411) 45-92 years of age. Serum leptin was measured in blood obtained between 1984 and 1987. Between 1988 and 1991, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA; at the same visit, height, weight, and body fat (by bioelectrical impedance analysis) were measured, and bone resorption was assessed in a subset of men (n = 286) and women (n = 241) using urine N-telopeptide (NTX). Four years later, axial BMD was remeasured in 536 participants. Sex-specific associations of leptin with BMD, NTX, and bone loss were tested using regression analysis. RESULTS: In unadjusted analyses, leptin was associated with BMD at the femoral neck, total hip, lumbar spine, and midshaft radius in both sexes (p < 0.01). In multiple regression analyses, adjusted for age, BMI, and other bone-related factors, only women showed a graded stepwise positive association between serum leptin and BMD at all sites and a negative stepwise association with NTX (all p for trend < 0.01). Baseline leptin levels did not predict 4-year bone loss in either sex. CONCLUSIONS: A favorable dose-dependent leptin-BMD association unexplained by obesity was observed only in women. The reason for the sex difference is unknown.     

Effect of alendronate on bone mineral density and bone turnover markers in post-gastrectomy osteoporotic patients

Alendronate decreases the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX; about 45% at 3 months) and serum levels of alkaline phosphatase (ALP; about 27% at 24 months), leading to an increase in lumbar spine bone mineral density (BMD; about 9% at 24 months) in postmenopausal Japanese women with osteoporosis. However, the effectiveness of oral bisphosphonates on osteoporosis remains to be established in patients who have undergone a gastrectomy. The objective of the present case series study was to examine the effect of alendronate on BMD and bone turnover markers in post-gastrectomy osteoporotic patients. Sixteen patients (3 men and 13 postmenopausal women) with osteoporosis, who had undergone a gastrectomy (mean age: 69.1 years), were recruited in our outpatient clinic. All the patients were treated with alendronate (5 mg daily or 35 mg weekly) for 24 months. The effects of alendronate on lumbar spine (women) or total hip (men) BMD and urinary NTX and serum ALP levels were examined. A total or partial gastrectomy had been performed for eight patients each. The mean duration after surgery was 16.0 years. With alendronate therapy, urinary NTX levels significantly decreased at 3 months (−27.0%). Serum ALP levels decreased (−12.1%) and lumbar spine BMD increased (+5.2%), but total hip BMD did not significantly change (+0.6%) at 24 months. No severe adverse events were observed, and alendronate therapy was well tolerated. These results suggest that alendronate mildly increases lumbar spine BMD by mildly reducing bone turnover in osteoporotic patients after a gastrectomy.     

Relationship among VDR (BsmI and FokI), COLIA1, and CTR polymorphisms with bone mass,bone turnover markers,and sex hormones in men

Osteoporosis is a disease characterized by low bone mineral density (BMD) and up to 80% of its variance is under genetic control. Although osteoporosis is more frequent in women, one-third of hip fractures also occur in men. Much information on genetic factors and bone density has been obtained in women, but only a few studies have been performed in osteoporotic men. We have evaluated the relationship between polymorphisms for several candidate genes such as vitamin D receptor (VDR), collagen type Ia1 (COLIA1), and calcitonin receptor (CTR) in a sample of unrelated Italian men (n = 253, mean age 58.41 +/- 15.64 SD). We found no significant differences in BMD when subjects were stratified for their VDR (BsmI and FokI) and COLIA1 genotypes. BMD both at the lumbar spine and at the femoral neck were associated with polymorphism of CTR gene. The CC genotype of CTR gene had the lowest BMD value (P <0.05 and P <0.01 at the spine and hip, respectively) and its prevalence was significantly over-represented in the subgroup of men with prior hip or vertebral fracture as compared with controls (P = 0.004% c2 = 11.10). The men with the CC genotype also showed significantly lower body mass index (BMI), serum sex hormone binding globulin (SHBG), estradiol, total alkaline phosphatase-(total AP) and bone alkaline phosphatase (bone AP) levels and significantly higher free androgen index (FAI). In conclusion, the polymorphism of CTR gene but not VDR and COLIA1 is associated with osteoporosis incidence and the levels of alkaline phosphatase and estradiol. The lower BMD in CC genotype is apparently associated in males with depressed bone formation and lower estradiol levels.     

Odanacatib in the treatment of postmenopausal women with low bone mineral density: Three‐year continued therapy and resolution of effect

The selective cathepsin K inhibitor odanacatib (ODN) progressively increased bone mineral density (BMD) and decreased bone‐resorption markers during 2 years of treatment in postmenopausal women with low BMD. A 1‐year extension study further assessed ODN efficacy and safety and the effects of discontinuing therapy. In the base study, postmenopausal women with BMD T‐scores between ?2.0 and ?3.5 at the lumbar spine or femur received placebo or ODN 3, 10, 25, or 50 mg weekly. After 2 years, patients (n = 189) were rerandomized to ODN 50 mg weekly or placebo for an additional year. Endpoints included BMD at the lumbar spine (primary), total hip, and hip subregions; levels of bone turnover markers; and safety assessments. Continued treatment with 50 mg of ODN for 3 years produced significant increases from baseline and from year 2 in BMD at the spine (7.9% and 2.3%) and total hip (5.8% and 2.4%). Urine cross‐linked N‐telopeptide of type I collagen (NTx) remained suppressed at year 3 (?50.5%), but bone‐specific alkaline phosphatase (BSAP) was relatively unchanged from baseline. Treatment discontinuation resulted in bone loss at all sites, but BMD remained at or above baseline. After ODN discontinuation at month 24, bone turnover markers increased transiently above baseline, but this increase largely resolved by month 36. There were similar overall adverse‐event rates in both treatment groups. It is concluded that 3 years of ODN treatment resulted in progressive increases in BMD and was generally well tolerated. Bone‐resorption markers remained suppressed, whereas bone‐formation markers returned to near baseline. ODN effects were reversible: bone resorption increased transiently and BMD decreased following treatment discontinuation. © 2011 American Society for Bone and Mineral Research.     

Preferential low bone mineral density of the femoral neck in patients with a recent fracture of the proximal femur

Bone mass is an important determinant of resistance to fractures. Whether bone mineral density (BMD) in subjects with a fracture of the proximal femur (hip fracture) is different from that of age-matched controls is still debated. We measured BMD of the femoral neck (FN) on the opposite side to the fracture, as well as femoral shaft (FS) and lumbar spine (LS) BMD by dual-photon absorptiometry in 68 patients (57 women and 11 men, mean age 78.8±1.0) 12.4±0.8 days after hip fracture following a moderate trauma. These values were compared with BMD of 93 non-fractured elderly control subjects (82 women and 11 men), measured during the same period. As compared with the controls, FN BMD was significantly lower in fractured women (0.592±0.013 v. 0.728±0.014 g/cm²,P<0.001) and in fractured men (0.697±0.029 v. 0.840±0.052,P<0.05). Expressed as standard deviations above or below the mean BMD of age and sex-matched normal subjects (Z-score), the difference in FN BMD between fractured women and controls was highly significant (–0.6±0.1 v. +0.1±0.1,P<0.001). As compared with mean BMD of young normal subjects, BMD was decreased by 36.9±1.4 and 22.4±1.5% (P<0.001) in fractured and control women, respectively. There was no significant difference between FN BMD of 33 women with cervical and 24 with trochanteric hip fractures (0.603±0.017 v. 0.577±0.020). FN BMD was lower than 0.705 g/cm² in 90% of fractured women. The prevalence of fracture increased with decreasing FN BMD, reaching 100% with values below 0.500 g/cm². FS and LS BMD were significantly lower in women with hip fracture than in controls (1.388±0.036 v. 1.580±0.030,P<0.001, for FS, and 0.886±0.027 v. 0.985±0.023,P<0.01, for LS), but these differences were not significant when expressed as a Z-score. In men with a recent hip fracture, FS BMD was significantly lower than in controls (1.729±0.096 v. 2.069±0.062,P<0.01), but the difference at the LS level did not reach statistical significance. These results indicate that both women and men with a recent hip fracture had decreased bone mineral density of the femoral neck, femoral shaft and lumbar spine. However, the difference appeared to be of higher magnitude for the femoral neck suggesting a preferential bone loss at this site.     

Effect of osteoarthritis in the lumbar spine and hip on bone mineral density and diagnosis of osteoporosis in elderly men and women

To determine in the elderly the effect of osteoarthritis on bone mineral density (BMD) and on diagnosis of osteoporosis, lumbar spine and hip were radiographed and BMD measured by dual-energy X-ray absorptiometry (DXA) in 120 men and 314 women, aged 60–99 years. Prevalence and severity of osteoarthritis were scored on osteophytes, joint space narrowing and bone sclerosis. Ultrasound measurements were also made at the heel to examine whether osteoarthritis at hip or lumbar spine influence bone at this remote site. Osteophytes were the commonest feature, with men having a higher prevalence than women, and lumbar spine having more disease than hip. Lumbar spine osteophytes affected 75% of men and 61.1% of women, and hip osteophytes affected 31.7% of men and 27.4% of women. Stepwise multiple regression analysis using age, weight, height, osteophytes, sclerosis and joint space narrowing indicated that lumbar osteophytes explained 16.6% of variation in lumbar spine BMD in women, and 22.4% in men. Hip osteophytes had a minimal effect on hip BMD, accounting for only 2.2% of variation in women, and none in men. Sclerosis and joint narrowing had little effect on BMD at lumbar spine or hip. Indirect effects of osteoarthritis on BMD were small and inconsistent across genders. Lumbar spine osteophytes in men explained 3.1% of hip BMD variation and 6% of variation in speed of sound at the heel, whereas hip osteophytes in women explained 2.2% of lumbar spine BMD variation. Osteoporosis at the hip, defined as BMD <2.5 SD of the young normal mean, was present in 33.1% of women and 25.8% of men, whereas, at the lumbar spine it was present in only 24.2% of women and 4.2% of men. However, in women and men free of spinal osteoarthritis, 37.7% of women and 10% of men had osteoporosis. We conclude that lumbar spine ostoephytes affect most subjects over the age of 60 years, and contribute substantially to lumbar spine BMD measured in the anteroposterior position by DXA. The effect is largely direct by virtue of osteophytes being included in the BMD measurement. However, a small indirect effect on remote skeletal sites is also present. Diagnosis of osteoporosis and assessment of osteoporotic fracture risk in the elderly should be based on hip BMD and not on anteroposterior lumbar spine, unless spinal osteoarthritis has been excluded.     

Sexual differences in bone markers and bone mineral density of normal Chinese

We measured bone mineral density (BMD) at lumbar (L2–L4) vertebrae and proximal femurs of 385 healthy Chinese women aged 40–70 years and 156 healthy Chinese men aged 20–85, and four markers—bone alkaline phosphatase isozyme (BAP), procollagen-I C terminal propeptide (PICP), osteocalcin (BGP) in serum, and a bone resorption marker, urinary cross-linked N-telopeptide of type I collagen (NTX), of these subjects. The results indicate that in postmenopausal women, levels of all the markers increased with age. In men, serum BAP, PICP, and urinary NTX decreased significantly, and serum BGP decreased with borderline significance (P=0.08). With increasing age, bone density decreased at both sites in post-menopausal women and at the proximal femur in men. The lumbar bone density showed no significant age-related changes in men. In premenopausal women, BMD at either site showed no significant change with increasing age. Despite the different trends between men and women of agerelated changes in BMD and bone markers, bone density of both proximal femur and spine in both sexes correlated inversely with levels of the bone markers in a manner independent of age or body weight. The meaning of opposite age effects on bone markers in men and women needs further investigation. In addition, higher bone marker levels, implying faster bone turnover rate, are associated with lower BMD in both sexes.     

中老年男性不同部位骨密度和骨质疏松检出率的对比分析

目的探讨中老年男性在应用双能X线骨密度仪检测不同部位骨密度时应关注检测的部位。方法选取2012年9月至2014年12月在我院行双能骨密度检测的中老年男性,比较腰椎、髋部、前臂桡骨下1/3的骨密度(BMD)和T值。结果中老年男性腰椎、髋部、前臂桡骨下1/3三个部位的BMD和T值比较,P0.001差异有统计学意义。随着年龄逐渐增大,腰椎BMD和T值下降不明显,髋部、前臂BMD和T值60岁以后才逐渐降低,前臂T值下降幅度明显大于腰椎和髋部。随着年龄的增加,髋部及前臂骨质疏松检出率也逐渐增加,但腰椎骨质疏松检出率随年增加反而下降。结论应用双能X线骨密度仪检测腰椎、髋部、前臂3个部位,经比较发现老年男性髋部和前臂BMD和T值明显低于腰椎,而且腰椎BMD和T值相对平稳,提示对老年男性骨质疏松诊断应同时检测髋部和前臂骨密度,以免出现骨质疏松的漏诊。     

Bone mass and mineral metabolism in HIV+ postmenopausal women

The objective of this cross-sectional study was to estimate the prevalence of and risk factors for osteoporosis in HIV+ postmenopausal women. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) and biochemical indices of mineral metabolism were measured in 31 Hispanic and African American HIV+ postmenopausal women. BMD was compared with 186 historical controls, matched for age, ethnicity and postmenopausal status. Mean BMD was significantly lower at the lumbar spine and total hip in the HIV+ group, as compared with controls. Prevalence of osteoporosis was higher in the HIV+ group than controls at the lumbar spine (42% vs 23%, p =0.03) and total hip (10% vs 1%, p =0.003). Among HIV+ women, time since menopause and weight were significant predictors of BMD, while duration or class of antiretroviral therapy (ART), AIDS diagnosis, nadir CD4, steroid use, and vitamin D deficiency were not. Prevalence of osteoporosis is substantially higher in HIV+ Hispanic and African-American postmenopausal women than in controls. Established osteoporosis risk factors were more important in predicting BMD than factors associated with HIV infection and ART. Long-term management of the growing female HIV population should include the evaluation for and management of osteoporosis.     

Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial

INTRODUCTION: Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor-kappa B ligand (RANKL), an essential mediator of osteoclast formation, function, and survival that has been shown to decrease bone turnover and increase bone mineral density (BMD) in treated patients. We assessed the long-term efficacy and safety of denosumab, and the effects of discontinuing and restarting denosumab treatment in postmenopausal women with low bone mass. METHODS: Postmenopausal women with a lumbar spine T-score of -1.8 to -4.0 or proximal femur T-score of -1.8 to -3.5 were randomized to denosumab every 3 months (Q3M; 6, 14, or 30 mg) or every 6 months (Q6M; 14, 60, 100, or 210 mg); placebo; or open-label oral alendronate weekly. After 24 months, patients receiving denosumab either continued treatment at 60 mg Q6M for an additional 24 months, discontinued therapy, or discontinued treatment for 12 months then re-initiated denosumab (60 mg Q6M) for 12 months. The placebo cohort was maintained. Alendronate-treated patients discontinued alendronate and were followed. Changes in BMD and bone turnover markers (BTM) as well as safety outcomes were evaluated. RESULTS: Overall, 262/412 (64%) patients completed 48 months of study. Continuous, long-term denosumab treatment increased BMD at the lumbar spine (9.4% to 11.8%) and total hip (4.0% to 6.1%). BTM were consistently suppressed over 48 months. Discontinuation of denosumab was associated with a BMD decrease of 6.6% at the lumbar spine and 5.3% at the total hip within the first 12 months of treatment discontinuation. Retreatment with denosumab increased lumbar spine BMD by 9.0% from original baseline values. Levels of BTM increased upon discontinuation and decreased with retreatment. Adverse event rates were similar among treatment groups. CONCLUSIONS: In postmenopausal women with low BMD, long-term denosumab treatment led to gains in BMD and reduction of BTM throughout the course of the study. The effects on bone turnover were fully reversible with discontinuation and restored with subsequent retreatment.