Protein intake, malnutrition, and its association with bone health after a hip fracture: A 3-month prospective study

The significance of high bone density in children

About two thirds of patients with a procollagen type I N-terminal propeptide (PINP) increase of >80 μg/l at 1 month after starting teriparatide therapy showed a ≥10 % increase in lumbar spine (LS) bone mineral density (BMD) from baseline at 12 months. We recommend this algorithm as an aid in the clinical management of patients treated with daily teriparatide. An algorithm using PINP is provided in osteoporotic patients with teriparatide treatment. The correlations between the early changes in PINP and the subsequent BMD changes after daily teriparatide therapy were studied to develop an algorithm to monitor patients. We evaluated whether early changes in PINP correlated with the changes in BMD at 12 months and developed an algorithm using the early changes in PINP to predict the upcoming BMD increases. The highest correlation coefficient for the relationship between PINP and LS BMD response was determined for the absolute change in PINP at 1 month and the percent change in LS BMD at 12 months (r = 0.36, p <0.01). Using a receiver operator curve analysis, we determined that an 80 μg/l increase in PINP was the most convenient predictor of a 10% increase in LS BMD from baseline (area under curve = 0.72). Using a cut-off value of 80 μg/l, the positive predictive value for predicting a 10% increase in LS BMD from baseline to 12 months was 65%. Greater short-term changes in PINP with teriparatide therapy are associated with greater 12-month increases in LS BMD. About two thirds of patients with a PINP increase of >80 μg/l at 1 month after starting treatment showed a ≥10 % increase in LS BMD from baseline at 12 months. We recommend this algorithm as an aid in the clinical management of patients treated with teriparatide.

Disclosure: J.P. Brown: Advisory Board Member; Self; Amgen Inc. Consulting Fee; Self; Amgen Inc, Gilead, Paladin, Pfizer, Inc., Servier. Research Investigator; Self; Mereo BioPharma, Radius Health, Inc, Servier. Speaker; Self; Amgen Inc. Other; Self; Ultragenyx. R.A. Adler: Grant Recipient; Self; Radius Health, Inc. E.M. Lewiecki: Consulting Fee; Self; Amgen Inc, Radius Health, Inc, Kyowa Kirin, Angitia, Ascendis. Research Investigator; Self; Amgen Inc, Radius Health, Inc, Ultragenyx. Speaker; Self; Amgen Inc, Kyowa Kirin. N. Binkley: Consulting Fee; Self; Amgen Inc, Radius Health, Inc. Research Investigator; Self; Amgen Inc, Radius Health, Inc. E.S. Orwoll: Consulting Fee; Self; Amgen Inc, Angitia, Biocon, Radius Health, Inc, Ultragenyx. Y. Wang: Employee; Self; Radius Health, Inc. D.L. Kendler: Consulting Fee; Self; Amgen Inc, Radius Health, Inc. Grant Recipient; Self; Amgen Inc, Radius Health, Inc. Speaker; Self; Amgen Inc, Radius Health, Inc. B.H. Mitlak: Employee; Self; Radius Health, Inc. R. Eastell: Consulting Fee; Self; Immunodiagnostic Systems, Sandoz, Samsung, CL Bio, Biocon, Takeda, UCB. Grant Recipient; Self; Alexion Pharmaceuticals, Inc.. Speaker; Self; Pharmacosmos, Alexion Pharmaceuticals, Inc., UCB, Amgen Inc. Background: Early serum procollagen type I N-terminal propeptide (PINP) increases correlate with 18-month lumbar spine (LS) bone mineral density (BMD) increases in postmenopausal women; however, this relationship has not been assessed in men. The Abaloparatide for the Treatment of Men with Osteoporosis (ATOM; NCT03512262) study demonstrated that abaloparatide (ABL) treatment in men with osteoporosis rapidly increased BMD at the LS, total hip (TH), and femoral neck (FN) compared with placebo (PBO). Bone turnover markers (BTMs), PINP and serum carboxy-terminal cross-linked telopeptide of type I collagen (CTX), were measured during the study. In this analysis, the correlation of early increases in BTMs and increases in BMD at 12 months between the ABL and PBO groups were determined and the results in men were compared to 12-month results in women from the ACTIVE study. Methods: ATOM was a randomized, double-blind, placebo-controlled, multicenter phase 3 study. A total of 228 men aged 40 to 85 years with osteoporosis or osteoporosis associated with hypogonadism were randomized 2:1 to receive 80 µg subcutaneous daily ABL or PBO for 12 months (ABL, n=149; PBO, n=79). Blood samples were collected under fasting conditions at baseline and post-dose at 1, 3, 6, and 12 months, and PINP and CTX measured. The correlation of increase from baseline in PINP and CTX concentrations, measured by log ratio over baseline, was compared with percentage increase from baseline BMD at 12 months using Spearman’s rank correlation. To compare between men and women, Pearson correlation coefficients were assessed using the z score test after Fischer’s Z transformation. Results: In the ABL group, median PINP level was 48.2 ng/mL at baseline, peaked at month 1 (109.0 ng/mL) and was 85.7 ng/mL at month 12. Median CTX level was 0.327 ng/mL at baseline, peaked at month 6 (0.476 ng/mL) and was 0.448 ng/mL at month 12. The increase in BTMs relative to baseline were significantly greater at all time points compared to PBO (P&amp;lt;0.0001). Median levels of PINP and CTX in men and women were similar over 12 months. Early PINP increases and subsequent LS BMD increases were significantly correlated for ABL in men starting at month 1, with the strongest correlations observed between 3 and 6 months. The correlation at 3 months was considered more clinically relevant, and the correlation coefficient in men receiving ABL (r=0.6138; P&amp;lt;0.0001) and women receiving ABL (r=0.561; P&amp;lt;0.0001) at 3 months are similar. Additionally, there was a significant correlation between the 1-month log ratio of PINP and TH BMD in men receiving ABL (r=0.1903; P&amp;lt;0.05). Conclusion: In the ATOM study, there was a significant correlation between early increases of BTMs (1 and 3 months) and BMD increases at 12 months. The correlation between early increases in PINP and percentage increase in LS BMD after 12 months of treatment with ABL in men is similar to that reported in women. Presentation: 6/2/2024

Bone loss and increased bone turnover are recognized local changes after a fracture, but the exact patterns of these changes after different fractures are unclear. We aimed to investigate the changes in bone density and biochemical markers following ankle fracture. Fourteen subjects (7 postmenopausal women and 7 men, mean age 63 years) were recruited following fracture of the distal tibia and fibula. Bone mineral density (BMD) of the ankle and proximal femur were measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) of the calcaneus at 0, 6, 12, 26 and 52 weeks after fracture. Serum and urine samples were collected at 0, 3 and 7 days and at 2, 4, 6, 12, 26 and 52 weeks after fracture to measure markers of bone turnover. For bone formation we measured: bone alkaline phosphatase (iBAP), osteocalcin (Oc), procollagen type I N-terminal propeptide (PINP); and for bone resorption: tartrate-resistant acid phosphatase (TRAcP), deoxypyridinoline (iFDpd), N-telopeptides of type I collagen (NTx). We used the nonfractured limb to calculate values for baseline BMD and QUS. There was a significant decrease in BMD at the ultradistal ankle (p<0.001), the trochanteric region of the hip (p<0.01) and QUS of the heel after ankle fracture. This bone loss was maximal for ultradistal ankle BMD by 6 weeks at 13% (p<0.001) and for the trochanter by 26 weeks at 3% (p<0.01). The ankle BMD returned to baseline at 52 weeks but the trochanter BMD did not. Velocity of sound (VOS) decreased at 6 weeks by 2% (p<0.01) and broadband ultrasound attenuation (BUA) by 15% (p<0.01). VOS recovered completely by 52 weeks, but BUA did not return to baseline. Bone formation markers increased significantly between 1 and 4 weeks by 11-78% (p<0.01), and iBAP returned to baseline at 52 weeks but PINP and Oc remained elevated. Bone resorption markers did not increase and NTx was decreased at 52 weeks. We conclude that BMD decreased distal and immediately proximal to the fracture line when measured with DXA and QUS. Ankle BMD and heel VOS recovered at 52 weeks (trochanteric BMD and heel BUA did not) and the bone turnover markers returned toward baseline.

Aims: To review the effects of bisphosphonates on bone density, fractures, and bone markers in osteopenic older women.Methods: Relevant articles published before February 2022 were searched in PubMed, EMBASE, and the Cochrane Library. All randomized controlled trials that reported incident fractures, bone mineral density (BMD), bone markers, or adverse events with bisphosphonates in osteopenic older women were included. The quality of included studies was assessed using the Cochrane Risk of Bias tool. The risk ratios (RRs) for fractures, net percent change in bone mineral density and differences in bone markers were calculated using a meta-analysis.Results: A total of 11 studies were included in our meta-analysis. Bisphosphonates significantly increased the percent changes in the lumbar spine BMD (WMD, 5.60; 95% CI, 4.16–7.03; I2 = 93.6%), hip BMD (WMD, 4.80; 95% CI, 2.93 to 6.66; I2 = 97.1%), total body BMD (WMD, 3.24; 95% CI, 2.12–4.35; I2 = 90.9%), femoral neck BMD (WMD, 4.02; 95% CI, 1.70–6.35; I2 = 91.8%) and trochanter BMD (WMD, 5.22; 95% CI, 3.51–6.93; I2 = 83.6%) when compared to placebo. Zoledronate was associated with a great treatment effect on fragility fracture (RR, 0.63; 95% CI, 0.50–0.79), clinical vertebral fracture (RR, 0.41; 95% CI, 0.22–0.76), and radiographic vertebral fracture (RR, 0.60; 95% CI, 0.27–1.35) compared to placebo. Meanwhile, alendronate was also associated with beneficial effects on fragility fracture (RR, 0.40; 95% CI, 0.15–1.07), clinical vertebral fracture (RR, 0.46; 95% CI, 0.17–1.24), and radiographic vertebral fracture (RR, 0.64; 95% CI, 0.38–1.09). In addition, the use of bisphosphonates reduced the concentration of procollagen type I N-terminal propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX) over placebo by 15.79 (95% CI, −18.92 to −12.66; I2 = 28.4%), −0.23 (95% CI, −0.35 to −0.10; I2 = 91.3%), respectively. Although there was insufficient evidence to determine their safety, these bisphosphonates may have an effect on cancer, cardiac events, and mortality in osteopenic older women.Conclusion: All bisphosphonates examined were associated with beneficial effects on fractures, BMD, and bone markers in women with osteopenia. Further randomized controlled trials are necessary to clarify the safety of bisphosphonates in women with osteopenia.

When and how should bone mineral density be measured?

BackgroundOsteoporosis is a major health problem of elders. Dual X-ray absorptiometry (DEXA) is the commonly used modality for diagnosis osteoporosis; serum markers have been suggested for predicting osteoporosis and discriminate osteoporotic from healthy subjects. We aimed to analyze the status of some bone turnover biochemical markers namely PINP, B-ALP, estrogen, and progesterone in the elderly osteoporotic and osteopenic women as probable markers for the discrimination between patients and healthy individual in diagnosing osteoporosis, and also, to detect the impact of osteoporosis on quality of life of patients using assessment of the quality of life for osteoporosis (ECOS-16). Post-menopausal 108 females were involved in the current study, divided into two groups (osteoporotic group (60 with BMD˂-2.5), osteopenic group (48 with BMD between − 1 and − 2.5)), and 60 healthy elderly females as control group were involved in the study. Serum levels of procollagen type I N-terminal propeptide (PINP), bone alkaline phosphatase (B-ALP), estrogen, and progesterone were measured by ELISA technique.ResultsPINP and B-ALP significantly differ between studied groups. Also, PINP and B-ALP levels had high sensitivity and specificity to discriminate osteoporotic patients from healthy individuals. PINP and B-ALP significantly correlated with bone mineral density (BMD) and with ECOS-16. Estrogen differs significantly between osteoporotic and osteopenic groups and significantly correlated with bone mineral density of femur (BMD-F) and bone mineral density of spine (BMD-S) in the osteopenic group. Progesterone differed significantly between patients and controls and significantly correlated with BMD-F in the osteoporotic group.ConclusionWe can consider PINP and B-ALP as biomarkers for early detection then monitoring of osteoporosis. Measuring these serum markers can replace the assessment of BMD if not available. Also, it could replace the gap between BMD subsequently spaced assessment or could be of value in cases with severe spondylosis, DISH syndrome, old spondylarthritis, and/or previous spinal surgery. Sex hormones could not differentiate the normal from the osteoporotic/osteopenic patients, so they cannot be used as diagnostic or prognostic markers. Validation of this assumption needs large and longitudinal studies.

Discriminative ability of calcaneal quantitative ultrasound compared with dual-energy X-ray absorptiometry in men with hip or distal forearm fractures

Objective To examine the relationship between plasma soluble interleukin 2 receptor(sIL2R), bone metabolism markers, and bone mineral densities in female patients with Graves′ disease(GD), and to explore the role of sIL2Rin bone metabolism of GD. Methods This study included 201 female GD patients. FT3,FT4,TSH, PTH, osteocalcin(OCN), C-terminal telopeptides of type Ⅰ collagen (CTX), procollagen type I N-terminal propeptide(PINP), and 25-(OH)-vitamin D(25OHD)were measured using electrochemical luminescence technique.sIL2R was measured using chemiluminescence method. All pations underwent examinations of bone mineral densities at lumbar spine, total hip, and femoral neck(LS-BMD, TH-BMD, and FN-BMD). The associations of sIL2R with bone metabolism markers and bone mineral densities were analyzed. Results OCN, CTX, PINP gradually decreased across the tertile groups of LS-BMD, TH-BMD, FN-BMD(all P<0.05). FT3,sIL2R gradually increased across the tertile groups of OCN, CTX, PINP(all P<0.05). Multiple linear regression analysis showed that sIL2R was independently associated with OCN and CTX(both P<0.05). Conclusion The increase of bone turnover leads to bone loss in female GD patients. The plasma level of sIL2R was positively correlated to bone turnover, which indicated that sIL2R may play an important role in bone metabolism of GD. (Chin J Endocrinol Metab, 2017, 33: 382-386) Key words: Graves′ disease; Soluble interleukin 2 receptor; Thyroid function; Bone mineral density; Bone metabolism

Effects of Raloxifene on Bone Metabolism in Hemodialysis Patients

SummaryLess is known about recovery from hip fracture in men. We found differences in 25-hydroxyvitamin D and bone biomarkers between men and women during the year after hip fracture, underscoring the importance of vitamin D assessment in older men and pharmaceutical treatment to reduce bone resorption after hip fracture.PurposeLess is known about recovery from hip fracture in men compared to women. We examined differences between men and women in 25-hydroxyvitamin D (25OHD) and bone turnover markers, and associations with bone mineral density (BMD) and physical function, during the year after a hip fracture.MethodsCommunity-dwelling, ambulatory adults aged 65 years and over (157 men and 154 women) enrolled in the Baltimore Hip Studies 7th cohort were included. We analyzed 25OHD, C-terminal telopeptide (β-CTX-I), procollagen type I N-terminal propeptide (PINP), PTH, and femoral neck BMD at baseline, 2, 6, and 12 months after hip fracture, and short physical performance battery (SPPB) at 2, 6, and 12 months.ResultsDuring admission for hip fracture, median 25OHD levels were 15.2 ng/mL (IQR 10.0) in men compared with 23.9 ng/mL (IQR 13.4) in women and remained lower in men at 2, 6, and 12 months (all p < 0.001). β-CTX-I was higher in men on admission, and at 2 and 6 months (all p < 0.05), and PINP was higher in men at 6 months (p = 0.04), with no significant differences between men and women in PTH. Higher 25OHD and PINP concentrations in women only and lower β-CTX-I and PTH concentrations in both sexes were associated with greater BMD. Higher 25OHD concentrations were associated with higher SPPB scores in both sexes.ConclusionsThese findings underscore the importance of vitamin D assessment in older men and missed opportunities in both sexes for vitamin D supplementation and pharmaceutical treatment to reduce bone resorption after hip fracture.

Quantitative ultrasound parameters as well as bone mineral density are better predictors of trochanteric than cervical hip fractures in elderly women. Results from the EPIDOS study

Response to Levin Letter

To study the association of quantitative ultrasound (US) parameters and bone mineral density (BMD) in patients with and patients without recent fractures. The authors studied 4,698 women (69 years or older) who had sustained 1,363 new fractures, including 106 hip fractures, during the 7 years prior to the study. Broadband ultrasound attenuation (BUA) and other velocity parameters were measured by means of quantitative US of the calcaneus. BMD was measured at the spine, hip, and calcaneus. The standardized age-adjusted odds ratio for all fractures was 1.5 (95% confidence interval [CI] = 1.4, 1.7) for BUA and up to 1.6 (95% CI = 1.5, 1.7) for BMD. For hip fractures, the odds ratio was 1.9 (95% CI = 1.5, 2.4) for BUA and up to 2.6 (95% CI = 2.0,3.4) for BMD. Sensitivity and specificity with BUA, velocity parameters, and BMD were comparable. Results of multivariate analysis showed that both BUA and BMD were independently associated with fractures and that combined measurements improved sensitivity and specificity. Quantitative US parameters are strongly associated with risk of fracture and partly independent of BMD. This simple, low-cost, portable, and radiation-free approach may complement bone densitometry in assessing risk of osteoporotic fracture.

Axial BMD in Diabetic and Nondiabetic Southeast Asians with HIP Fractures: Do Race and Body Mass Index Matter?