Mean Bone Mineral Density Loss Research Articles

Treatment of endometriosis-associated pain with linzagolix, an oral gonadotropin-releasing hormone–antagonist: a randomized clinical trial

To study the effect of a new investigational oral gonadotropin-releasing hormone antagonist, linzagolix, on endometriosis-associated pain (EAP). A multinational, parallel group, randomized, placebo-controlled, double-blind, dose-ranging trial. Clinical centers. Women aged 18-45 years with surgically confirmed endometriosis and moderate-to-severe EAP. The interventions were 50, 75, 100, or 200 mg linzagolix (or matching placebo) administered once daily for 24 weeks. The primary endpoint was the number of responders (≥30% reduction in overall pelvic pain) after 12 weeks. Other endpoints included dysmenorrhea, non-menstrual pelvic pain, serum estradiol, amenorrhea, quality of life (QoL) measures, and bone mineral density (BMD). Compared with placebo, doses ≥ 75 mg resulted in a significantly greater proportion of responders for overall pelvic pain at 12 weeks (34.5%, 61.5%, 56.4%, and 56.3% for placebo, 75, 100, and 200 mg, respectively). A similar pattern was seen for dysmenorrhea and non-menstrual pelvic pain. The effects were maintained or increased at 24 weeks. Serum estradiol was suppressed, QoL improved, and the rate of amenorrhea increased in a dose-dependent fashion. Mean BMD loss (spine) at 24 weeks was <1% at doses of 50 and 75 mg and increased in a dose-dependent fashion up to 2.6% for 200 mg. BMD of femoral neck and total hip showed a similar pattern. Linzagolix significantly reduced EAP and improved QoL at doses of 75-200 mg and decreased BMD dose-dependently. NCT02778399.

Bone Mineral Density in Relation to Chronic Kidney Disease After Heart Transplantation: A Retrospective Single-center Study at Skåne University Hospital in Lund 1988-2016.

Background.Our aim was to investigate the bone mineral density (BMD) evolution and incidence of osteoporosis in relation to chronic kidney disease (CKD) up to 10 years after heart transplantation (HT).Methods.A retrospective analysis was performed on 159 HT patients at Skåne University Hospital in Lund 1988–2016.Results.The median follow-up time was 6.1 years (interquartile range = 7.5 y). HT patients with CKD stage <3 or normal kidney function before HT exhibited a greater mean BMD loss in the lumbar spine, compared to patients with CKD stage ≥3 before HT, at the first (−6.6% versus −2.5%, P = 0.029), second (−3.7% versus 2.1%, P = 0.018), and third (−2.0% versus 4.1%, P = 0.047) postoperative years, respectively. All included HT patients exhibited a BMD loss in the femoral neck at the first postoperative year (−8.8% [−10.3 to −7.3] in patients with CKD stage <3 or normal kidney function and −9.3% [−13.2 to −5.5] in patients with CKD stage ≥3 before HT), which was not fully reversed up to 10 years after HT. In adjusted models, CKD stage <3 before HT did not predict osteopenia and osteoporosis in the lumbar spine or femoral neck.Conclusions.CKD before HT did not predict BMD loss or osteoporosis development after HT. The study is, however, limited by a lack of data on fractures, and further studies on the relationship between CKD and postoperative bone strength are encouraged.

Hip bone loss is attenuated with 1000 IU but not 400 IU daily vitamin D3: A 1-year double-blind RCT in postmenopausal women

Few year-long vitamin D supplementation trials exist that match seasonal changes. The aim of this study was to determine whether daily oral vitamin D3 at 400 IU or 1000 IU compared with placebo affects annual bone mineral density (BMD) change in postmenopausal women in a 1-year double-blind placebo controlled trial in Scotland. White women aged 60 to 70 years (n = 305) were randomized to one of two doses of vitamin D or placebo. All participants started simultaneously in January/February 2009, attending visits at bimonthly intervals with 265 (87%) women attending the final visit and an additional visit 1 month after treatment cessation. BMD (Lunar iDXA) and 1,25-dihydroxyvitamin D[1,25(OH)2 D], N-terminal propeptide of type 1 collagen [P1NP], C-terminal telopeptide of type I collagen [CTX], and fibroblast growth factor-23 [FGF23] were measured by immunoassay at the start and end of treatment. Circulating PTH, serum Ca, and total 25-hydroxyvitamin D [25(OH)D] (latter by tandem mass spectrometry) were measured at each visit. Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group (0.05% ± 1.46%) compared with the 400 IU vitamin D or placebo groups (0.57% ± 1.33% and 0.60% ± 1.67%, respectively) (p < 0.05). Mean (± SD) baseline 25(OH)D was 33.8 ± 14.6 nmol/L; comparative 25(OH)D change for the placebo, 400 IU, and 1000 IU vitamin D groups was -4.1 ± 11.5 nmol/L, +31.6 ± 19.8 nmol/L, and +42.6 ± 18.9 nmol/L, respectively. Treatment did not change markers of bone metabolism, except for a small reduction in PTH and an increase in serum calcium (latter with 1000 IU dose only). The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome, nor how much vitamin D is being stored.

Bone mineral density changes in pregnancies with gestational hypertension: a longitudinal study using quantitative ultrasound measurements

ObjectiveTo compare the maternal bone mineral density (BMD) changes in gestational hypertensive and normotensive pregnancies using quantitative ultrasound.MethodsConsecutive patients were recruited from a general obstetric clinic over a period of 9 months. BMD measurements were performed at the os calcis in early pregnancy before 20 weeks and in the late third trimester after 36 weeks, using a Hologic Sahara Clinical Bone Sonometer system. These patients were followed up in accordance with standard antenatal protocol. The diagnosis of gestational hypertension (GH) was made based on a standard institutional protocol. The changes in BMD from early to late pregnancy were compared between those with/without GH.ResultsA total of 450 patients with complete data were analyzed. The overall incidence of GH was 4.8% (n = 22), of which 1.7% (n = 8) fulfilled the definitions of severe pre-eclampsia. A mean BMD loss of 0.0256 g/cm2 (around 4.5% of early pregnancy BMD) was demonstrable from early to late gestation. The hypertensive group has marginally higher mean BMD loss as compared to the normotensive group (0.052 vs. 0.037 g/cm2; P = 0.037). However, regression analysis models showed that early pregnancy BMD values, early pregnancy fat percentage and fat accumulation in pregnancy were significant factors affecting BMD loss during pregnancy, while GH was not in the equations.ConclusionThe development of gestational hypertensive disorders apparently does not have any significant impact on BMD changes during pregnancy.

Back Pain Symptoms and Bone Mineral Density Changes in Pregnancy as Measured by Quantitative Ultrasound

Objective: To evaluate whether back pain symptoms in pregnancy are associated with bone mineral density (BMD) changes as measured by quantitative ultrasound at the os calcis. Methods: Consecutive patients were recruited from a general obstetric clinic over 1 year. Quantitative ultrasonographic measurements of BMD were performed at the os calcis between weeks 14–20 and 36–38. They were then surveyed for back pain symptoms experienced during pregnancy in the early postpartum period, and these were subsequently correlated with BMD changes. Results: Of a total of 463 patients, 231 (49.8%) reported one or more episodes of significant back pain during pregnancy. A mean fall in BMD of 0.0395 g/cm² was demonstrable from early to late gestation. Those with back pain symptoms have higher mean BMD loss at the os calcis during pregnancy compared to those without back pain (0.038 vs. 0.029 g/cm²; p = 0.012). A logistic regression model showed that weight gain and BMD loss in pregnancy were significantly associated with back pain symptoms. Conclusion: Back pain symptoms in pregnancy were associated with a greater fall in BMD at the os calcis, supporting the hypothesis that BMD changes could have an etiological role in back pain during pregnancy.

Bone mineral density changes in gestational diabetic pregnancies–a longitudinal study using quantitative ultrasound measurements of the os calcis

To compare the maternal bone mineral density (BMD) changes in gestational diabetic and non-diabetic pregnancies using quantitative ultrasound measurements of the os calcis, BMD measurements were performed at the os calcis in early pregnancy before 20 weeks and in the late third trimester after 36 weeks, using a Hologic Sahara Clinical Bone Sonometer system. Random glucose screening and direct oral glucose tolerance testing were used to diagnose gestational diabetes mellitus (GDM) according to World Health Organization criteria, which was then treated according to a standard protocol. In a cohort of 480 patients, there were 96 gestational diabetic patients (14 GDM and 82 with impaired glucose tolerance). The mean BMD loss was higher in diabetic patients compared with controls (0.038 vs. 0.025 g/cm2, p = 0.048). A regression model of all pregnancies showed that higher fat accumulation was related to lower BMD loss, but diabetic status was not in the equation. Within diabetic pregnancies, lower initial BMD values, higher fat accumulation and higher early-pregnancy body mass index were associated with lower BMD loss. While gestational diabetic women had higher BMD loss than non-diabetic women, this was apparently secondary to other anthropometric factors rather than due directly to the gestational diabetic state.

Comparative study of the protective effect of different intravenous bisphosphonates on the decrease in bone mineral density in patients submitted to radical prostatectomy undergoing androgen deprivation therapy. A prospective open‐label controlled study

To establish whether androgen deprivation therapy (ADT) promotes osteoporosis and osteopenia Ninety-four prostatectomized men with rising prostrate-specific antigen (PSA) were enrolled into the placebo group (31), monthly i.v. clodronate (39) or monthly i.v. zoledronic acid (24) groups for 36 months. Dual-energy X-ray absorptiometry measured the bone density in the lumbar (L2-L4) area. chi(2) and anova tests were used to analyze data.. After 6 months of androgen deprivation, 17 of the 31 control cases developed osteopenia in the lumbar area. At 12 months, nine control cases had osteoporosis with 13 additional cases of osteopenia. At the end of the 36-month study period, the untreated group showed an average bone mineral density (BMD) loss of -1.82 (+/-0.94) with 13 cases of osteopenia and 18 cases of osteoporosis. The clodronate group had two cases of osteoporosis out of 39 subjects after 6 months of ADT with 28 developing osteopenia and seven cases of osteoporosis after 36 months of follow up. Mean BMD loss in this group was -0.72 (+/-0.34). The zoledronic acid studied arm had seven cases of osteopenia after 6 months of ADT while 20 and five cases developed osteopenia and osteoporosis, respectively, after 36 months of follow up. The former group had a mean bone loss of -0.88 (+/-0.32). There was statistical difference for BMD loss in the treated groups starting at 6 months in comparison to the control group. Six months of ADT promoted impressive bone loss in the lumbar area of the non-treated patients. This tendency is progressive and may be delayed by i.v. bisphosphonates.

A prospective, controlled study of the effects of hormonal contraception on bone mineral density

OBJECTIVE: To compare the effect of depot medroxyprogesterone acetate (DMPA) and two types of oral contraceptives (OC) on bone mineral density (BMD) among women 18–33 years of age with those not using hormonal contraception. METHODS: Data from 155 women were analyzed. Depot medroxyprogesterone acetate was administered to 33 women; 63 women who chose oral contraception were randomly assigned to receive either a norethindrone-containing pill ( n = 28) or a desogestrel-containing pill ( n = 35). Fifty-nine women who did not use hormonal contraception served as controls. Lumbar spine BMD was determined using dual-energy x-ray absorptiometry at baseline and after 12 months of contraceptive use. We analyzed method-related percent change in BMD while controlling for body mass index, calcium intake, exercise, and smoking. We had approximately 90% power to detect a 2.5% difference between any two groups. RESULTS: Users of DMPA experienced a mean BMD loss of 2.74% over 12 months compared with controls who sustained a 0.37% loss ( P = .01). Users of OCs generally demonstrated a gain (2.33% for norethindrone-containing pills, 0.33% for desogestrel-containing pills), which was different from controls among users of norethindrone-containing pills ( P = .01), but not among users of desogestrel-containing pills ( P = .99). Observed changes in BMD among DMPA users differed from women who used either type of pill ( P < .002). CONCLUSION: Depot medroxyprogesterone acetate has an adverse effect on BMD, in comparison with OCs or nonhormonal methods, when used for 12 months. Results must be interpreted cautiously until it is determined whether these effects endure or are reversible.

Ambulatory level and asymmetrical weight bearing after stroke affects bone loss in the upper and lower part of the femoral neck differently: bone adaptation after decreased mechanical loading

The aim of this 1-year prospective study of acute stroke patients was to determine the effects of walking and asymmetrical weight bearing on the loss of bone mineral in the upper and lower femoral neck. Forty patients were followed. Eight remained unable to walk, whereas 32 relearned to walk independently within 7 months (12 shortly after the stroke, 15 by 2 months, 5 by 7 months). Bone mineral density (BMD) was measured in the proximal femur within the first week after stroke and 1 year later; regional BMD changes were computed for the lower and upper femoral neck. The lower part of the femoral neck is mainly influenced by compressive stresses of the hip, the upper part by tensile stresses during walking. When comparing mean BMD loss in groups of patients according to when they relearned to walk, a statistically significant trend in BMD loss was found in the lower femoral neck on both the paretic and nonparetic sides ( p < 0.01 and p = 0.01, respectively), whereas, for the upper femoral neck, no significant trend was seen ( p ≥ 0.1). In addition, the body weight distribution during standing was assessed by use of a force-plate in 38 patients who could stand independently at the 7 month evaluation. The only significant correlation between changes in BMD and asymmetrical weight bearing was found in the lower femoral neck on the paretic side ( r = 0.6, p < 0.001). In conclusion, this study shows that the reduction in BMD in the femoral neck occurs mainly in the lower part of the neck and on the paretic side. The BMD loss depended on when or if the patients relearned to walk, but also on the amount of body weight born on the paretic leg. Thus, measuring the lower part of the femoral neck gives a better estimate of the impact of gait and weight bearing than measuring the total femoral neck.

Detailed analyses of periarticular osteoporosis in rheumatoid arthritis.

Periarticular osteopenia is the earliest radiographic sign of rheumatoid arthritis (RA). Recent studies using dual-energy X-ray absorptiometry (DXA) have indicated that the loss of periarticular BMD can be quantified by whole-hand bone mineral density (BMD) measurements. The aim of this study was to analyze periarticular BMD in more detail by DXA and quantitative ultrasound (QUS). In a cross-sectional study 23 women aged 30-76 years with early RA, mean disease duration 26 +/- 19 months, and 18 men aged 42-69 years, mean disease duration 24 +/- 25 months, were examined. All patients received antirheumatic therapy. The reference population consisted of 103 age-matched controls (68 females, 35 males) and young healthy controls. BMD measurements were performed using a DXA Expert XL densitometer (Lunar). BMD of the whole-hand and two subregions was determined: two subchondral regions of interest (S.CH.) were set within the trabecular bone, distal to the proximal interphalangeal joints of digits II and III excluding the dense subchondral bone of the metacarpophalangeal (MCP) joint and two metacarpal regions of interest (MCP) were set including the entire MCP joint of these fingers. QUS measurements at the proximal phalanges of digits II-V were performed using a DBM Sonic (Igea); amplitude-dependent speed of sound (Ad-SoS) was determined. In comparison with whole-hand BMD measurements, bone loss was pronounced in patients with a disease duration of 18-72 months at the subchondral regions of interest in both genders compared with age-matched controls (women: mean BMD loss S.CH. -23%, p<0.001, whole-hand -16%, p<0.001; men: mean BMD loss S.CH. -19%, p < 0.05, whole-hand -12%, p<0.05). The bone changes were also shown by QUS (women: Ad-SOS values of 1950 +/- 90 m/s in RA vs 2137 +/- 35 m/s in young healthy controls (p <0.005); men AD-SOS 1956 +/- 87 m/s in RA vs 2146 +/- 41 m/s in young healthy controls (p <0.05)). These results show that BMD and Ad-SOS values are significantly lowered in patients with early RA and indicate that periarticular osteoporosis in early RA might possibly be better detected using detailed hand scan analyses.

Generalised bone loss in patients with early rheumatoid arthritis

Summary Generalised osteoporosis is a feature of established rheumatoid arthritis but whether this is a consequence of treatment, immobility, or disease activity has been unclear. We estimated bone mineral density by dual energy x-ray absorptiometry on 148 patients with early rheumatoid arthritis before treatment with corticosteroids or disease-modifying drugs and 730 normal controls. Scans were done at 12-month intervals in patients and at 0 and 12 months on 50 of the controls matched for menopausal status. At presentation, bone mineral density of patients did not differ from controls. However, patients with disease for less than 6 months had significantly higher spinal bone mineral density than those of longer duration. Over the next 12 months, bone mineral density loss was greater in patients with rheumatoid arthritis compared with controls; significantly so for early disease (eg, -2·4 [0 8] vs -0·6 [0·4] g/cm 2, p<0·05 in the spine and -4·3 [0·8] vs -0·4 [0·5] g/cm 2, p<0·001 in the trochanter). For the lumbar spine, only disease activity was significantly associated with this bone mineral density loss. For patients with active disease over 2 years, mean bone mineral density loss at each site was between 5 5 and 10% (p<0·01 compared to patients with inactive disease). Suppression of disease activity stabilised this bone loss. In patients with rheumatoid arthritis significant amounts of generalised skeletal bone were lost early in the disease and the loss was associated with disease activity. These findings have implications for the management of patients with rheumatoid arthritis and possibly other inflammatory diseases.