Mission of Osteos

To enhance state-of-the-

art knowledge and expert

care for osteoporosis and

other metabolic bone

disorders in Lebanon

through education, research

and service.

OSTEOS NEWSLETTER Newsletter of the Lebanese Society for Osteoporosis and Metabolic Bone Disorders

Editor-in-Chief: Asma Arabi, MD, MSc Guest Editor Hala Ahmadieh, MD

President

Rafic Baddoura, MD, MPH

Founding President

Ghada El-Hajj Fuleihan, MD, MPH

Vice-President

Muhieddine Seoud, MD

Secretary

Walid Saghir, MD

Treasurer

Jad Okais, MD

Executive Committee

Ghada El-Hajj Fuleihan, MD, MPH

Faisal El-Kak, MD

Georges Halaby, MD

Assaad Mohanna, MD

Jad Okais, MD

Walid Saghir, MD

Imad Uthman, MD

To join OSTEOS please

visit our website:

http://www.osteos.org.lb

For your suggestions,

please contact us:

osteos@osteos.org.lb

Read in this Issue

Highlights from the ASBMR annual meeting. o Calcium supplements intake and cardiovascular

risk. o The WHI Calcium plus Vitamin D Supplementation

Trial. o Dietary calcium intake and fractures. o Bone loss following bypass surgery. o Skeletal effect of hyperglycemia & glucose

lowering therapies. o Skeletal effect of reducing inflammation in

diabetes.

PPI and non vertebral fractures.

Antidepressants and bone health.

Updates on osteoporosis in men. o Bisphosphonates and glucocorticoid osteoporosis in

men. o Fracture risk and zoledronic acid therapy in men. o Treatment of osteoporosis in men.

Time to onset of efficacy in fracture reduction.

Normocalcmic hyperparathyroidism.

Densitometry corner.

Mark your calendar for upcoming meetings.

Issue No 5.3

Fall 2012

Welcome Note

Dear Colleagues,

I would like to welcome you all to this new edition of OSTEOS Newsletter. As usual, our aim is to

keep you well-informed of the most recent updated news that relate to osteoporosis and other

metabolic bone disorders, which will help in achieving our vision of providing the best health care

possible to all of those we serve. This newsletter provides a unique opportunity for networking

with different members in different specialties. As in previous editions, this newsletter will

provide you with selected abstracts from the annual meeting of the American Society for Bone

and Mineral Research that was held in Minneapolis last October. You will also find very

interesting updates and news with regards to different topics including hyperparathyroidism, PPI

and bone health in addition to updates on osteoporosis particularly in men. Dear colleague, you are

very precious to us and you have encouraged us to bring to you the best possible news.

Hala Ahmadieh, MD.

SELECTED ABSTRACTS FROM THE 34th

ANNUAL MEETING OF THE

AMERICAN SOCIETY FOR BONE AND MINERAL RESEARCH

Calcium Supplement Intake and Cardiovascular Risk Disease in Women.

Presentation 1135, by Paik J et al.

“We conducted a prospective analysis of the relation between calcium supplement intake and the risk of CVD in a cohort of 74,272 women participating in the Nurses’ Health Study (1984-2006) who were free of CVD and cancer at baseline. Calcium supplement intake was assessed every four years by semiquantitative food-frequency questionnaires. CVD outcomes were defined as CHD (nonfatal MI or fatal CHD) and stroke (nonfatal or fatal). During 22 years of follow-up, 4,857 cardiovascular events occurred (2,634 CHD and 2,223 stroke events). The age-adjusted relative risk of CVD was 0.67 (95% CI 0.62, 0.72) for women taking >500mg/day of calcium supplements (8.5% at baseline) compared to no calcium supplements. After multivariable adjustment for age, vitamin D intake, and other CVD risk factors, the relative risk of CVD for women taking

>500mg/day of calcium supplements compared to no calcium supplements was 0.88 (95% CI 0.81, 0.95; p for trend <0.001). For cumulative average calcium supplement intake and CVD risk, the relative risk of CVD was 0.92 (95% CI 0.84, 1.02) for women taking >500mg/day compared to no calcium supplements. For calcium supplement use and CHD risk, the multivariable-adjusted relative risk of CHD in women taking >500mg/day compared to no calcium supplements was 0.83 (95% CI 0.74, 0.93; p for trend <0.001). For cumulative average calcium supplement intake and CHD risk, the relative risk of CHD was 0.88 (95% CI 0.76, 1.01) for women taking >500mg/day compared to no calcium supplements. In our study, calcium supplements were not associated with increased cardiovascular risk, including MI, in women”.

The Women’s Health Initiative (WHI) Calcium plus Vitamin D Supplementation Trial: Health

Outcomes 5 years after Trial Completion. Presentation 1136, by Cauley et al

“The WHI Calcium plus Vitamin D supplementation trial assessed whether 1000 mg of elemental calcium with 400 IU of vitamin D3 (CaD) vs placebo reduced the risk of hip fracture and colon cancer in 36,282 women who were age 50 to 79 yrs at study entry. After an average of 7 yrs of follow-up, modest, albeit non-significant, reductions were observed for hip, clinical vertebral and total fracture. Coronary heart disease (CHD) and cancer incidence was similar in the 2 groups. Total mortality was slightly lower in the CaD group. The objective of the current analysis was to determine the effects of CaD on outcomes over 7 yrs (trial) and 5 additional yrs of follow-up through September 2010. Follow-up continued after the planned trial completion among 86% of surviving participants, CaD, n=15025 and placebo, n=14837. Primary outcomes were identified from annual mailed questionnaires and adjudicated centrally. Hip fracture was the only fracture adjudicated in the overall period; all other fractures were self-reported. All analyses were intent-to-treat. All participants were included in the analysis according to their randomized group assignment until last contact. The post-intervention risk (annualized rate) of hip fracture among women randomized to CaD

was 0.28% compared with 0.30% in the placebo group, hazard ratio (HR)=0.95; 95% confidence interval (CI) ( 0.78, 1.15); 0.36% vs 0.43%, respectively for clinical vertebral fractures, HR=0.83; 95% CI (0.71, 0.98); 3.31% vs 3.30%, respectively, for total fractures HR=1.00; 95% CI (0.94, 1.06), (see Table). The risk of invasive colorectal cancer was non-significantly lower among women randomized to CaD in the post-intervention period, HR=0.80; 95% CI (0.61, 1.07), while the risk of breast cancer was slightly elevated, HR=1.17; 95% CI (0.99, 1.38), p=0.06. Total cancers did not differ between the CaD and placebo groups. There was no difference in CHD and total and cardiovascular disease mortality by randomized group in the post-intervention period. In the overall period, no significant differences between treatment groups were observed except that vertebral fractures were 13% lower among women randomized to CaD vs placebo, HR=0.87; 95% CI (0.76, 0.98). In conclusion, among postmenopausal women followed for up to 12 yrs, CaD was associated with a decreased risk of vertebral fractures, but, had little effect on the other skeletal and non-skeletal outcomes”.

Associations of Long-term Dietary Calcium Intake with Fractures, Cardiovascular Events and

Aortic Calcification in a Population-based, Prospective Cohort Study. Presentation 1227 by Khan et al.

Differential Bone Loss Following Gastric Surgery: Comparison of Different Modalities at 12 Months. Presentation 1224, by Brzozowska et al.

“Obesity rates have increased markedly in recent decades. Gastric surgery is the most effective therapy. However, the skeletal consequences are not fully elucidated. We examined the skeletal response to 3 weight loss modalities: Medical Managed Dieting (MDD), Gastric Banding (GB) and Gastric Sleeve (GS). We present preliminary 12 mth data from a 24 mth prospective trial. In addition to DXA at 0 and 12 mths, data were collected for calcium intake, 25-OH D, PTH, gut hormones and adipokines. There were 10 MMD, 4 GB and 20 GS subjects. At baseline, average age was 51±12 yrs (MMD 56±10, GB 44±14, GS 51±13, ns). BMI was 40±7 (MMD 38±7, GB 37±5, GS 43±6, ns). Calcium intake, 25-OH D and PTH were normal. However, 25% of subjects had an osteopenic/osteoporotic DXA Z-score. At 12 mths, differences in response were evident between groups. % weight change was small in MMD (-6: -7,-0.7), greater in GB (-15: -17,-13) and greatest in GS (-29: -33,-21), P<0.0001. (Median: Q1,Q3), ANOVA. Despite weight loss among groups, % changes in total hip BMD were evident only in GS(-6: -8,-5) but minimal in MDD(-0.7: -1.9,0.3) and GB(-0.3: -0.6,0), P<0.0005. We examined factors affecting bone loss:

1. In GS, all weight loss occurred in the first 6 mths post-surgery, however bone loss was ongoing: 3.5% by 6 mths, 6% by 12 mths. Moreover the 2 patients with 24 mth data had further bone loss to 11.6% suggesting that weight loss is not the sole determinant of bone loss.

2. Bone turnover markers increased in GS from baseline to 12 mths: osteocalcin (8±3 µg/L to 14±9, P<0.002) and uNTX (28± 12nmol/mMCr to 55± 24, P<0.02) with no change in MDD and GB.

3. Calcium intake, vitamin D and PTH were normal throughout. 4. Gut-derived, pro-satiety hormone Peptide YY increases post-meal to reduce appetite and has a

negative effect on bone. At baseline no PYY response was evident in any group. At 12 mths, %PYY increase at 90 minutes (median: Q1, Q3) was MMD (23.7: 13.8, 48.7), GB (34.4: 9.5, 87.1), GS(121.6: 65.3,187.4), P<0.01. GLP-1 response was not significantly altered. Adiponectin increases matched weight loss MMD (6.6: -2.1, 13.6), GB (27: 5.6, 50.6), GS (51.9: 33.7, 87.7), P<0.0005. Different weight loss modalities produced varied skeletal responses. Bone loss was marked in GS but absent in GB despite weight loss. Bone loss post-GS may involve changes in PYY and adiponectin, in addition to weight loss”.

“Objectives:To determine associations between dietary calcium intake and risk of fractures, cardiovascular events, mortality,

vertebral deformities and aortic calcification. Design: Prospective cohort study of 41,514 men and women aged 45-64 years followed 13-14 years for mortality, incident fractures and cardio-vascular events. 12,528 were eligible for fracture analysis, and 37,253 for cardiovascular and mortality analyses. A subset, having dietary calcium intakes of <500 mg/day (n=172) or ³1300 mg/day (n=174) at baseline, had lateral thoraco-lumbar spine x-rays. Outcome measures (whole cohort): Cumulative self-reported incident fractures, non-fatal cardiovascular events (CVE), and mortality. Dietary calcium intake was assessed at baseline using a validated food frequency questionnaire and quartiles of energy-adjusted dietary calcium intake (CIQ) defined. Hazard ratios (HR) for mortality and odds ratios (OR) for self-reported events were calculated using Cox and logistic regression. In the subset, abdominal aortic calcification score (ACS, 24 point scale) and vertebral deformities (SQ method) were measured from x-rays. Linear, ordinal logistic and logistic regression measured coefficients for ACS; spinal deformity index (SDI) and OR for tertiles of AAC; and OR for ACS (≥6) and moderate to severe vertebral deformities.Results: 824 (10.4%) reported incident fractures, 2,674 (12.9%) had incident non-fatal cardiovascular events; and 3,445 (9.3%) deaths occurred. After adjusting for potential confounders, the OR for incident fracture was 0.75 (CI 0.60-0.94) for the highest compared with lowest CIQ. The OR for incident CVE was 0.84 (CI 0.74-0.96); the OR for incident stroke was 0.87 (CI 0.62-0.97) and HR for all-cause mortality was 0.90 (CI 0.81-1.00) in the highest CIQ. In the subset, 103 (29.8%) had a vertebral deformity of which 36 (10.4%) were moderate to severe. AAC was present in 229 (66.2%) and 115 (33.2%) had ACS of ≥6. The OR for vertebral deformity was 0.41 in the high dietary CI group (CI 0.25-0.68), including moderate to severe deformities (OR 0.33, CI 0.15-0.74). The SDI coefficient was also lower (-0.19, CI -0.33 to -0.05) and OR for severe aortic calcification (ACS≥6) was 0.41 (CI 0.17-0.99). Results were similar when dietary calcium unadjusted for energy was used. Conclusion: Higher dietary calcium intakes are beneficial to health and associated with decreased risks for all fractures, non-fatal cardiovascular events, stroke and vertebral deformity”.

Diabetes Mellitus and Osteoporosis; Skeletal Effects of Diabetic Hyperglycemia and Glucose

Lowering Anti-diabetic Therapies. Presentation 1226, by Lecka-Czernik et al.

The Skeletal Effects of Reducing Inflammation in Type 2 Diabetes Mellitus Presentation 1216, by Donovan et al.

“The skeleton is now recognized, epidemiologically, to be adversely affected in Type 2 Diabetes (T2D), with an increased risk of fractures. Previous studies have identified reduced bone formation as a contributing factor, but the mechanisms remain speculative. One possible explanation is chronic inflammation, which negatively influences bone remodeling by reducing bone formation and increasing bone resorption. The Targeting INflammation using SALsalate in Type 2 Diabetes (TINSAL-T2D) trial found that a salicylate, which reduces inflammation by decreasing NF-κB, improved glycemic control in patients with T2D. We hypothesized that reducing inflammation in T2D would additionally lead to a rebalancing of the bone remodeling process. In TINSAL-T2D patients were randomized to placebo (PLB) or salsalate, at doses of 3.0, 3.5 or 4.0 g/d tid for 14 weeks. We measured markers of bone turnover (P1NP, BAP, osteocalcin, s-CTx and TRAP-5b) in samples from TINSAL-T2D at 0 and 14 weeks. 76 subjects with T2D (56±1yr, 51 men, BMI 33±1 kg/m2, 43% Caucasian, HbA1c 7.6±1%; none on TZDs or insulin) were analyzed. At baseline, corrected

serum calcium was 9.2 ±1 mg/dl; PTH 35±1 pg/ml; 25OHD 21±2 ng/dl. Baseline P1NP was 36.8±2 ng/ml (nl: 16-83), BAP 28.3±1 IU/L (nl:11.6-29.6), osteocalcin 10.7±1 ng/ml (nl: 8.4-33.9), s-CTx 0.29±0.1 ng/ml (nl: 0.11 – 0.74) and TRAP-5b 3.2±0.1 U/L (nl:1.03-4.15). With salsalate treatment, P1NP, BAP and TRAP-5b did not change, but osteocalcin increased from 0 to 14 wks at the highest dose as compared with PLB (PLB: -3%±9% vs. 4 mg dose: 34%±8%, p=0.003). Moreover, s-CTx levels increased from 0 to 14 wks at the 3.5 mg dose (PLB: 7± 3 vs 3.5 mg dose: 95 ±19%, p=0.003), tending also to increase at the 4 mg dose (31 ±22%; p=0.16 vs PLB). These data suggest that along with reductions in inflammation and glycemic burden in TINSAL-T2D, there is an increase in bone remodeling, as reflected by increases in osteocalcin and s-CTx. Although one would not expect that bone resorption would increase with a concomitant reduction in NF-κB, there may be a coupled rise in bone remodeling in T2D as inflammation is reduced. This study provides proof of concept for a relationship between the inflammatory process and skeletal dynamics in T2D”.

“Osteoporosis and diabetic disease have reached epidemic proportion and create significant public health concerns. The

prevalence of these diseases is alarming, and indicates that in the US, 50% of elderly individuals are osteoporotic and almost

20% of population has either diabetic or prediabetic conditions. Diabetes mellitus and osteoporotic fractures are two of the

most important causes of mortality and morbidity in older individuals. There is a close association between fragility fracture

risk and diabetes mellitus, which not necessarily correlates with a reduced bone mineral density (BMD), however it

correlates with a reduced biomechanical quality of the bone. Osteoporosis and diabetes share many features including

genetic predispositions and molecular mechanisms. This concurs with recent findings indicating that bone status is closely

linked to regulation of energy metabolism and insulin sensitivity. Indeed, bone and energy homeostasis are under the

control of the same transcriptional and hormonal factors, including the peroxisome proliferator activated receptor gamma

(PPAR?), pancreatic hormone - insulin, hormones produced by adipose tissue - leptin and adiponectin, gastrointestinal

hormones including ghrelin, glucose inhibitory protein (GIP) and glucagon inhibitory peptide (GLP), and bone derived

hormone osteocalcin. These factors and related mechanisms control glucose homeostasis and fatty acids metabolism in

peripheral tissues, which are pharmacological targets for anti-diabetic therapies. The same factors may contribute to the

bone quality by their effect on bone cell differentiation and bone remodeling process creating a possibility that glucose

lowering drugs may have adverse effects on bone. The review of skeletal effects of available anti-diabetic therapies indicate

that they may either increase fracture risk (TZDs and insulin), or may not affect the risk (sulfonylurea), or may even decrease

the risk (metformin and incretins). In conclusion, the linkage between osteoporosis and diabetes is multifactorial”.

DRUG INDUCED BONE LOSS

Use of proton pump inhibitors and risk of fragility hip fracture in a Mediterranean region, by Reyes C et al. Bone 52 (2013) 557–561

There has been an emerging concern over the last few years with regards to a possible harmful effect of proton pump inhibitors (PPI) on bone health, but the association was not well established. Reyes et al conducted a retrospective multi-center case–control study in six primary health care centers in Catalonia, Spain, that aimed at determining whether there is an increase of risk of hip fracture with the intake of PPI in a Mediterranean area. 358 cases aged 50 years or older (mean 82 years) with a fragility hip fracture were matched by sex and age with 698 controls. Females represented 77% of case and of controls. Information was obtained regarding the use of PPI (type, dosage) in the 5 years previous to the hip fracture, socio-demographic data, body mass index, alcohol and tobacco consumption as well as health conditions and drugs associated with an increased risk of fragility hip fracture. A 1.4 fold increased risk of hip fracture was found with the use of PPI but after adjustment for potential confounders, this relationship lost significance. This lack of association did not change when restricting the analysis by continuous or discontinuous consumption of PPI, by different doses, by different types of PPI, or by age or sex categories. This study concluded that use of PPI was not associated with an increased risk of hip fracture after adjusting for other risk factors in a Mediterranean area, suggesting the existence of protective environmental factors linked to this area that eventually could compensate for the potential harm produced by PPI.

Risk of nonvertebral fractures among elderly postmenopausal women using antidepressants. Rabenda V et al. Bone 51 (2012) 674–679.

Studies have shown an increased risk of bone fractures in patients receiving antidepressants. Several mechanisms have been proposed but their potential effects on bone metabolism remain incompletely understood. Previous studies that examined the relationship between use of these medications and risk of fractures used data from administrative databases and in consequence have been limited by their ability to control for potential confounding factors. Moreover most of the data focused mainly on hip fractures. In this post-hoc analysis of pooled data from two international, phase III, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis Therapeutic Intervention[SOTI] and TReatment Of Peripheral OSteoporosis [TROPOS]), Rabenda et al examined the association between antidepressants and the risk of non-vertebral fractures (NVF) among women with osteoporosis. These datasets contain accurate data about fractures and about confounding factors known to influence bone outcomes, such as depression, BMD, previous fractures, lifestyle (smoking, alcohol),or concomitant drugs that may cause fractures. Nested case‐control study was performed in the placebo treated population. After 3 years of follow-up, 391 NVF were identified. Antidepressants use was associated with an increased risk of NVF [adjusted OR=1.64; 95%CI, 1.03–2.62]. There was specifically a 2-fold risk increase (95%CI, 1.07–3.79) of NVF for current users of SSRIs and a 2.1-fold risk increase for current users of TCAs (95%CI, 1.02–4.30). These findings confirmed the increased risk of NVF in current users of both SSRIs and TCAs.

UPDATES ON MALE OSTEOPOROSIS

Bisphosphonates and glucocorticoid osteoporosis in men: results of a randomized controlled trial comparing zoledronic acid with risedronate. Sambrook P et al, Bone 50 (2012) 289–295

Glucocorticoids use has been associated with rapid bone loss and increased risk of fragility fractures especially within the first few months of therapy, even when started at low doses. Bisphosphonates, due to their anti-resorptive effects, are recommended as the first-line treatment for the prevention and treatment of glucocorticoid induced osteoporosis (GIO), however, most of the trials included postmenopausal women and only a few included small proportions of men. This multinational, multicenter, randomized, double-blind, double-dummy 1-year study compared the efficacy of Zoledronic acid (ZOL) and Risedronate (RIS) in preventing GIO in 265 men, aged 18–85 years, initiating or continuing on high-dose glucocorticoids therapy (≥7.5 mg/ day of prednisolone or equivalent). Patients were randomized (1:1) to receive a single ZOL 5 mg i.v. infusion or oral RIS 5 mg daily for 1 year. In addition, all patients received supplemental calcium (1000 mg) and vitamin D (400–1200 IU) daily Prevention” subpopulation (patients using high-dose glucocorticoid therapy for ≤3 months or less) and “treatment” subpopulation (patients using high-dose glucocorticoid therapy for >3 months) were both included. In the treatment subpopulation, Lumbar spine BMD (LSBMD) increased by 4.7% with ZOL and by 3.3% with RIS (p=0.02 for difference between groups). In the prevention subpopulation, percentage changes in LSBMD were 2.5% and -0.2% for ZOL and RIS groups respectively (p=0.002 for difference between groups). In the treatment subpopulation, ZOL demonstrated a significantly greater reduction in serum β-CTx and P1NP relative to RIS at all time-points. In the prevention subpopulation, ZOL significantly reduced β-CTx at all time-points, and P1NP at Month 3 only. Both treatments were well tolerated in men, but a higher incidence of influenza-like illness and pyrexia events post-infusion with ZOL. In conclusion a single infusion of ZOL was associated with significantly greater increases in lumbar spine BMD and total hip BMD in men as compared to oral risedronate. Fracture Risk and Zoledronic Acid Therapy in Men with Osteoporosis. Boonen S et al, New Engl J Med 2012; 367;18

In a multicenter, double-blind, placebo-controlled 24 month trial, Boonen et al assessed the effect of intravenous infusion of zoledronic acid ( ZOL 5 mg) as compared to placebo, on the risk of vertebral fracture (VF) in 1199 men aged 50-85 years, with primary or hypogonadism-associated osteoporosis. Men were defined as osteoporotic if they had a BMD T score of –2.5 or less at the total hip (TH), femoral neck (FN), or lumbar spine (LS), or if they had a BMD T score of –1.5 or less at the TH or FN and one to three prevalent mild to moderate VF (VF were graded using the semiquantitative method of Genant). Participants were randomly assigned to either 5 mg ZOL or placebo at baseline and at 12 months of the study. In addition, all patients received daily calcium and vitamin D supplementation throughout the study. Over the 24 months period, the rate of any new morphometric VF was 1.6% in the ZOL group and 4.9% in the placebo group, representing a 67% significant risk reduction with ZOL. BMD was higher and bone-turnover markers were lower in the men who received ZOL. Results were similar in men with low serum levels of total testosterone. The ZOL and placebo groups did not differ with respect to serious adverse events. In conclusion, ZOL treatment was associated with a significantly reduced risk of VF among men with osteoporosis.

Treatment of Osteoporosis in Men.

Kaufman J et al. Bone 2012; doi: 10.1016/j.bone.2012.11.018

Osteoporosis has been for longtime considered as a disease of women only. Over the last decade, osteoporosis has emerged as an important public health problem in men. Recently, the Endocrine Society released its guidelines for the management of osteoporosis in men, and we reported these guidelines in the previous issue of our Newsletter. Recently, A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) workshop was convened to discuss osteoporosis in men. A debate with an expert panel on preselected topics was conducted and consensus views were reached on diagnostic criteria and intervention thresholds. We highlighted herein the main points of the report of the workshop that was published by the panel of experts in Bone.

About 4–6% of men over the age of 50 years have osteoporosis.

The patterns of bone loss in men seem to be different from those in women. Earlier trabecular loss was measured in men, with cortical loss starting after the age of 50 years, possibly linked to gonadal steroid decline.

The risk of hip and vertebral fracture is similar in men and women for any given BMD, supporting the use of a BMD value of 2.5 SD or more below the mean for young adult women for the diagnosis of osteoporosis in men.

Both in men and women, age, prior fracture and BMD capture a substantial proportion of fracture risk with further independent contribution of additional risk factors.

The question of whether markers of bone turnover predict accelerated bone loss or fractures in men remains unanswered.

The available level of evidence that treatment decreases the risk of fracture in men is lower than for Women. Additional fracture data are needed to endorse the clinical care of osteoporosis in men.

o The treatment response to oral bisphosphonates in male osteoporosis is similar to that observed in postmenopausal osteoporosis, in terms of bone density and bone remodelling. To date, conclusive antifracture evidence with alendronate and risedronate is unavailable in men, With iv zoledronic acid, a preliminary report of fracture endpoint data in osteoporotic men indicates that zoledronic

acid anti-fracture efficacy in men mirrored that observed in women. o Teriparatide studies concluded that the changes in biochemical markers, BMD, and vertebral fracture risk in response to 20

mcg teriparatide in men were essentially the same as in women. o Testosterone prevents bone loss and may increase bone mass in hypogonadal men, although there is little available long-

term data and no fracture data. o A hypogonadal man with a high risk of fracture should receive classical osteoporosis medication, regardless of whether

testosterone is being initiated on the basis of current hypogonadism treatment guidelines. o Estrogen or selective estrogen receptor modulators (SERMS) are currently not approved for use in men although low

estradiol levels were associated with high bone remodeling and bone loss in men. Serum-free estradiol but not testosterone, was independently associated with fracture risk in the MrOs study.

o A number of drugs with anti-fracture efficacy in postmenopausal women are available and are likely to be applicable in men, provided that bridging studies are carried out.

Available evidence suggests that treatment algorithms in women are also applicable to men. In practice, this is likely to involve the use of FRAX and clinical risk factors.

Men should be treated at a similar 10-year fracture risk as in women, because the morbidity and mortality associated with osteoporotic fractures in men are substantial.

Normocalcemic versus Hypercalcemic Primary Hyperparathyroidism: More Stone than Bone? Amaral L et al, Journal of Osteoporosis, 2012 doi:10.1155/2012/128352

Normocalcemic primary hyperparathyroidism (NPHPT) characterized by high PTH level but with a normal calcium is usually identified during the investigation of reduced bone density. This study retrospectively evaluated 70 patients with primary hyperparathyroidism [33 normocalcemic and 37 mild hypercalcemic]. Patients who had clinical manifestations of nephrolithiasis were evaluated by ultrasound. Bone fractures were confirmed by radiography. The prevalence of nephrolithiasis was 18.2% in the normocalcemic group and 18.9% in the hypercalcemic group, without difference between groups (P =0.9). Fifteen percent of the normocalcemic patients had a previous history of fractures compared to 10.8% of hypercalcemic patients, with no statistically significant difference (P =0.7). However, bone mineral density (BMD) of the distal radius was more preserved in the normocalcemic group than in the hypercalcemic group, although there were no significant differences in the lumbar spine and femoral neck BMD. This study data confirms a high prevalence of urolithiasis and of fractures in normocalcemic primary hyperparathyroidism despite preservation of cortical bone as compared to hypercalcemic patients. These findings support the hypothesis that NPHPT is not an idle condition and that this condition needs treatment.

Time to onset of efficacy in fracture reduction with current anti-osteoporosis treatments. Inderjeeth C et al. J Bone Miner Metab (2012) 30:493–503

Fragility fractures are associated with great morbidity and mortality. Effective evidence-based treatments are available for patients with osteoporosis. Because the time to onset of fracture efficacy is an important consideration when selecting antiosteoporotic drug, Inderjeeth C et al reviewed the onset of fracture efficacy data (including morphometric vertebral fracture (MVF), clinical vertebral fracture (CVF), nonvertebral fracture (NVF), hip fracture, and any clinical fracture (ACF)) on all of the commonly prescribed osteoporosis treatments, from available literature. In their report, they concluded that:

- - Alendronate was found to reduce multiple CVF by 6 months; all CVF, NVF, and multiple ACF by 12 months; and all ACF and hip fracture by 18 months.

- - Ibandronate reduced MVF by 12 months and NVF by 36 months. - - Raloxifene was found to decrease CVF by 3–6 months and NVF by 36 months. - - Risedronate was reported to reduce CVF and NVF by 6 months, and hip fracture by 12 months. - - Strontium ranelatereduced MVF, CVF, NVF, and ACF by 12 months, and hip fracture by 36 months. - - Zoledronic acid was reported to reduce MVF, CVF, and ACF by 12 months, NVF by 24 months, and hip fracture by 36 months.

Therefore, they concluded that risedronate, followed by alendronate, had the earliest onset of benefit across the range of fracture types. Although this is an important review, the conclusion is limited by the lack of direct comparisons between drugs. A large head to head comparison trial between different antiosteoporotic drugs is needed to further study that effect.

a.

Ms KF, a 67 year old postmenopausal woman who was diagnosed with osteoporosis in November 2010 (picture 1). In November 2012, she came to your clinic with follow up BMD (picture 2). Upon checking her BMD scans and given the following values, what can we tell the patient regarding her BMD changes?

a. Your BMD is deteriorating because your T-score dropped from -5.5 to -6. b. Your BMD is deteriorating since your Z-Score dropped from -3.6 to -4.1 c. Your BMD is stable because the percent changes in BMD are not significant. d. We cannot compare BMD because they were done on different devices. e. We cannot compare BMD because the region of interest is not the same.

Date Region BMD T-Score Z-Score

November 2010 L1-L4 0.438 -5.5 -3.6

November 2012 L1-L4 0.387 -6.0 -4.1

Date Event Location

Jan 30-Feb 1, 22nd IOF Advanced Training Course on Osteoporosis Geneva-Switzerland http://www.iofbonehealth.org/advanced-training

April 4-7, 11th International Conference on Bone and Mineral Research & 13th International Osteoporosis Symposium

Guangzhou-China www.china-osteofound.org/english

April 17-20, European Congress on Osteoporosis & Osteoarthritis Rome-Italy http://www.ecceo13-iof.org/

June 15-18, 95th annual meeting of the Endocrine Society Moscone Center, San Francisco, CA http://www.endo-society.org/endo/

October 4-7, 35th annual meeting of the American Society for Bone and Mineral Research

Baltimore Convention Center-Baltimore-Maryland http://www.asbmr.org/meetings/annualmeeting.aspx

Densitometry Corner

Mark Your Calendar

Densitometry corner correct answer: e When comparing serial BMD measurements:

The region of interest should be the same. In our case, the follow up scan, L3 was mislabeled for L4.

It is not possible to quantitatively compare BMD between different devices without cross-calibration. Patients should be encouraged to do serial Bone density measurements at the same facility.

In our case, both scans were obtained on same DXA device

BMD changes [increase or decrease] should be reported based on percent changes in BMD calculated as follows: [new BMD-old BMD/old BMD] x100 and not T-score or Z-Score. Only changes that exceed the least significant changes of the facility should be considered significant. In our case the percent changes cannot be calculated because the region of interest is not the same.

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