Tag Archives: abstract

Caffeine Not Associated with Bone Loss in Postmenopausal Women

Abstract

Dietary caffeine intake and bone status of postmenopausal women.

Dietary caffeine intake has been suggested as a risk factor for bone loss in postmenopausal women. We measured the bone density of both hips and the total body in 138 healthy, postmenopausal women aged 55-70 y who had either never used hormone replacement therapy (HRT) or had used HRT for < 1 y. In this cross-sectional study, participants were stratified according to their reported current and long-time caffeinated beverage use into one of three groups: low [0-2 cups (180 mL, or 6 oz per cup) caffeinated coffee per day], moderate (3-4 cups caffeinated coffee per day), or high (> or = 5 cups caffeinated coffee per day). Caffeine intake was measured from diet records and by gas chromatography of each subject’s brewed, caffeinated beverages. No association between caffeine intake and any bone measurement was observed. The anthropometric and nutrient intakes of the three groups were similar. Compared with caffeine intake based on chemical analysis of brewed beverages, 3-d prospective food records and computer-assisted analysis overestimated caffeine intake by nearly two-thirds. In conclusion, the habitual dietary caffeine intake of this cohort of 138 postmenopausal women ranged from 0-1400 mg/d and was not associated with total body or hip bone mineral density measurements. This study does not support the notion that caffeine is a risk factor for bone loss in healthy postmenopausal women.

Lloyd T, Rollings N, Eggli DF, Kieselhorst K…
Am. J. Clin. Nutr. Jun 1997
PMID: 9174479 | Free Full Text

Caffeine with < 800mg Calcium May Accelerate Bone Loss

Abstract

Caffeine and bone loss in healthy postmenopausal women.

The effects of caffeine consumption on rates of change in bone mineral density (BMD) were examined in 205 healthy, nonsmoking, postmenopausal women. BMD of the spine and total body were measured by dual-energy x-ray absorptiometry, and dietary intakes by food-frequency questionnaire. Among women with calcium intakes above the median (744 mg/d), 1-y rates of bone change–adjusted for years since menopause, body mass index, physical activity, and baseline BMD–did not differ by caffeine intake. However, among women consuming less calcium, those with the highest caffeine intakes (> 450 mg/d) had significantly more bone loss (ANCOVA, P < 0.05) than did women consuming less caffeine (0-171 and 182-419 mg/d). Percent change in BMD by lowest to highest tertile of caffeine consumption was 0.26 +/- 2.74, 0.70 +/- 2.70, and -1.36 +/- 2.70 at the spine and -0.19 +/- 1.24, 0.23 +/- 1.23, and -0.68 +/- 1.25 at the total body. Daily consumption of caffeine in amounts equal to or greater than that obtained from about two to three servings of brewed coffee may accelerate bone loss from the spine and total body in women with calcium intakes below the recommended dietary allowance of 800 mg.

Harris SS, Dawson-Hughes B
Am. J. Clin. Nutr. Oct 1994
PMID: 8092093 | Free Full Text

Caffeine > 2.5 Cups of Coffee Increases Fracture in Framingham Study

Abstract

Caffeine and the risk of hip fracture: the Framingham Study.

Caffeine increases urinary calcium output and has been implicated as a risk factor for osteoporosis. The authors examined the effect of caffeine on hip fracture risk in 3,170 individuals attending the 12th (1971-1973) Framingham Study examination. Coffee and tea consumption, age, Framingham examination number, weight, smoking, alcohol consumption, and estrogen use were used to evaluate hip fracture risk according to caffeine intake. Hip fractures occurred in 135 subjects during 12 years of follow-up. Fracture risk over each 2-year period increased with increasing caffeine intake (one cup of coffee = one unit of caffeine, one cup of tea = 1/2 unit of caffeine). For intake of 1.5-2.0 units per day, the adjusted relative risk (RR) of fracture was not significantly elevated compared with intake of one or less units per day. Consumption of greater than or equal to 2.5 units per day significantly increased the risk of fracture. Overall, intake of greater than two cups of coffee per day (four cups of tea) increased the risk of fracture. In summary, hip fracture risk was modestly increased with heavy caffeine use, but not for intake equivalent to one cup of coffee per day. Since caffeine use may be associated with other behaviors that are, themselves, risk factors for fracture, the association may be indirect. Further studies should be performed to confirm these findings.

Kiel DP, Felson DT, Hannan MT, Anderson JJ…
Am. J. Epidemiol. Oct 1990
PMID: 2403108

Caffeine Not an Important Risk in Young Women

Abstract

Is caffeine associated with bone mineral density in young adult women?

By increasing the urinary excretion of calcium, caffeine consumption may reduce bone mineral density (BMD) and subsequently increase the risk for osteoporotic fracture. Although negative associations between caffeine consumption and BMD have been reported for postmenopausal women, in particular for those who consume low amounts of dietary calcium, the relation between caffeine and BMD in younger women is unclear. Therefore, we evaluated the association between caffeine consumption and BMD in a cross-sectional study of 177 healthy white women, age 19-26 years, who attended a Midwestern university.
Average caffeine intake (milligrams per day) was calculated from self-reports of the consumption of coffee, decaffeinated coffee, tea, colas, chocolate products, and select medications during the previous 12 months (mean caffeine intake = 99. 9 mg/day). BMD (grams per square centimeter) at the femoral neck and the lumbar spine was measured by dual-energy X-ray absorptiometry.
After adjusting in linear regression models for potential confounders, including height, body mass index, age at menarche, calcium intake, protein consumption, alcohol consumption, and tobacco use, caffeine consumption was not a significant predictor of BMD. For every 100 mg of caffeine consumed, femoral neck BMD decreased 0.0069 g/cm(2) (95% confidence in terval [CI] = -0.0215, 0. 0076) and lumbar spine BMD decreased 0.0119 g/cm(2) (95% CI = -0. 0271, 0.0033). No single source of caffeine was significantly associated with a decrease in BMD. Furthermore, the association between caffeine consumption and BMD at either site did not differ significantly between those who consumed low levels of calcium (< or =836 mg/day) and those who consumed high levels of calcium (>836 mg/day).
Caffeine intake in the range consumed by young adult women is not an important risk factor for low BMD.

Conlisk AJ, Galuska DA
Prev Med Nov 2000
PMID: 11071837

Higher Calories Benefits Hip Replacement Recovery

Abstract

Tight Calorie Control in geriatric patients following hip fracture decreases complications: a randomized, controlled study.

Optimizing nutritional intake has been recommended for geriatric patients undergoing hip-fracture surgery. Whether nutritional support guided by repeated measurements of resting energy requirements (REE) improves outcomes in these patients is not known.
A randomized, controlled, unblinded, prospective, cohort study comparing provision of energy with a goal determined by repeated REE measurements using indirect calorimetry, with no intervention. Oral nutritional supplements were started 24 h after surgery and the amount adjusted to make up the difference between energy received from hospital food and measured energy expenditure.
50 Geriatric patients were included in the study. Patients in the intervention group (n = 22) received significantly higher daily energy intake than the control group (n = 28) (1121.3 ± 299.0 vs. 777.1 ± 301.2 kcal, p = 0.001). This was associated with a significantly less negative cumulative energy balance (-1229.9 ± 1763 vs. -4975.5 ± 4368 kcal, p = 0.001). A significant negative correlation was found between the cumulative energy balance and total complication rate (r = -0.417, p = 0.003) as well as for length of hospital stay (r = -0.282, p = 0.049).
We have demonstrated that nutritional support actively supervised by a dietician and guided by repeated measurements of REE was achievable and improved outcomes in geriatric patients following surgery for hip fractures.

Anbar R, Beloosesky Y, Cohen J, Madar Z…
Clin Nutr Feb 2014
PMID: 23642400

Oral Calcitonin Phase 3 Trail

Abstract

A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: the Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) trial.

The Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) study was a randomized, double-blind, double-dummy, active- and placebo-controlled, multiple-dose, phase 3 study to assess the efficacy and safety of oral recombinant calcitonin for treatment of postmenopausal osteoporosis. A total of 565 women age 46 to 86 (mean 66.5) years were randomized (4:3:2) to receive oral recombinant salmon calcitonin (rsCT) tablets (0.2  mg/d) plus placebo nasal spray, synthetic salmon calcitonin (ssCT) nasal spray (200 IU/d) plus placebo tablets, or placebo (placebo tablets plus placebo nasal spray), respectively for 48 weeks. All women received calcium (≥1000  mg/d) and vitamin D (800 IU/d). Women randomized to oral rsCT had a mean ± SD percent increase from baseline in lumbar spine bone mineral density (BMD) (1.5% ± 3.2%) that was greater than those randomized to ssCT nasal spray (0.78% ± 2.9%) or placebo (0.5% ± 3.2%). Lumbar spine BMD change in those receiving nasal calcitonin did not differ from placebo. Oral rsCT treatment also resulted in greater improvements in trochanteric and total proximal femur BMD than ssCT nasal spray. Reductions in bone resorption markers with oral rsCT were greater than those observed in ssCT nasal spray or placebo recipients. Approximately 80% of subjects in each treatment group experienced an adverse event, the majority of which were mild or moderate in intensity. Gastrointestinal system adverse events were reported by nearly one-half of women in all treatment groups and were the principal reason for premature withdrawals. Less than 10% of women experienced a serious adverse event and no deaths occurred. Overall, oral rsCT was superior to nasal ssCT and placebo for increasing BMD and reducing bone turnover. Oral rsCT was safe and as well tolerated as ssCT nasal spray or placebo. Oral calcitonin may provide an additional treatment alternative for women with postmenopausal osteoporosis.

Binkley N, Bolognese M, Sidorowicz-Bialynicka A, Vally T…
J. Bone Miner. Res. Aug 2012
PMID: 22437792

From Tarsa Therapeutics’ web site:

Tarsa Therapeutics in conjunction with Unigene Laboratories has developed a once-daily oral tablet version of calcitonin. This proprietary technology prevents the degradation of calcitonin in the gastrointestinal system and assists its transit across the cells lining the intestine and into the bloodstream.

Review: Oral Calcitonin 2012

Abstract

Oral calcitonin.

Calcitonin is a hormone secreted by the C-cells of the thyroid gland in response to elevations of the plasma calcium level. It reduces bone resorption by inhibiting mature active osteoclasts and increases renal calcium excretion. It is used in the management of postmenopausal osteoporosis, Paget’s disease of bone, and malignancy-associated hypercalcemia. Synthetic and recombinant calcitonin preparations are available; both have similar pharmacokinetic and pharmacodynamic profiles. As calcitonin is a peptide, the traditional method of administration has been parenteral or intranasal. This hinders its clinical use: adherence with therapy is notoriously low, and withdrawal from clinical trials has been problematic. An oral formulation would be more attractive, practical, and convenient to patients. In addition to its effect on active osteoclasts and renal tubules, calcitonin has an analgesic action, possibly mediated through β-endorphins and the central modulation of pain perception. It also exerts a protective action on cartilage and may be useful in the management of osteoarthritis and possibly rheumatoid arthritis. Oral formulations of calcitonin have been developed using different techniques. The most studied involves drug-delivery carriers such as Eligen(®) 8-(N-2hydroxy-5-chloro-benzoyl)-amino-caprylic acid (5-CNAC) (Emisphere Technologies, Cedar Knolls, NJ). Several factors affect the bioavailability and efficacy of orally administered calcitonin, including amount of water used to take the tablet, time of day the tablet is taken, and proximity to intake of a meal. Preliminary results looked promising. Unfortunately, in two Phase III studies, oral calcitonin (0.8 mg with 200 mg 5-CNAC, once a day for postmenopausal osteoporosis and twice a day for osteoarthritis) failed to meet key end points, and in December 2011, Novartis Pharma AG announced that it would not pursue further clinical development of oral calcitonin for postmenopausal osteoporosis or osteoarthritis. A unique feature of calcitonin is that it is able to uncouple bone turnover, reducing bone resorption without affecting bone formation and therefore increasing bone mass and improving bone quality. This effect, however, may be dose-dependent, with higher doses inhibiting both resorption and formation. Because so many factors affect the pharmacokinetics and pharmacodynamics of calcitonin, especially orally administered calcitonin, much work remains to be done to explore the full pharmacologic spectrum and potential of calcitonin and determine the optimum dose and timing of administration, as well as water and food intake.

Hamdy RC, Daley DN
Int J Womens Health 2012
PMID: 23071417 | Free Full Text

Another successful way of formulating oral calcitonin is by using an acid-resistant enteric coating that prevents dissolution in the stomach and adding citric acid to the tablet core to inhibit intestinal proteases and enhance paracellular transport across the intestinal mucosa. This formulation also has been tested in Phase III studies.

Nasal Calcitonin No Benefit After Hip Replacement

Abstract

Salmon calcitonin (Miacalcic ns 200 IU) in prevention of bone loss after hip replacement.

Loosening of a hip prosthesis after total arthroplasty is related to periprosthetic bone loss. Calcitonin has been used in the treatment of bone loss in osteoporosis and prevention of fractures. The main purposes of the study were firstly to evaluate the effect of calcitonin on periprosthetic bone after total hip arthroplasty, secondly investigate possible loosening of the prosthesis and thirdly examine further clinical outcome.
60 patients who underwent total hip arthroplasty using cemented Exeter prosthesis were randomized in the treatment group (salmon calcitonin 200 IU nasal spray daily + calcium 500 mg) and the placebo group (inactive nasal spray + calcium 500 mg) for six months. Bone mineral density (BMD) was measured from different locations at the time of discharge and after six and 12 months. Dynamic histomorphometry on bone biopsies taken from femoral collum was performed. Serum bone-specific alkaline phosphatase (BAP), serum osteocalcine (OC) and cross-linked N-telopeptides (NTX) were measured after one week, one month, three months and 12 months. Clinical manifestations and the incidence of fractures and loosening of the prosthesis were followed up to eight years.
Statistically there was not significant difference in bone histomorphometry between the groups. In both groups there was a significant BMD decrease in periprosthetic bone. However, the difference between the groups was not statistically significant. In the biochemical analysis NTX increased more in the Miacalcic group than in the placebo group (p = 0.013). There were no significant differences between the groups in serum BAP or OC even though the changes within the groups were statistically significant. No loosening of the prosthesis was seen during the follow-up and there was no need for revision of any reason. Four fractures were recorded in three patients. One patient sustained a periprosthetic fracture. All the patients with fractures were allocated in the placebo group.
Nasal salmon calcitonin 200 IU on a daily basis does not promote any additional value on calcium substitution to prevent bone loss after hip replacement. The durability of the Exeter prosthesis was good.

Arnala IO
Scand J Surg 2012
PMID: 23238499 | Free Full Text

Review: Data do Not Support Use of Nitroglycerin

Abstract

Nitroglycerin ointment for the prevention of postmenopausal osteoporosis.

To determine whether clinical trial data support the use of nitroglycerin for prevention of postmenopausal osteoporosis.
A literature search using MEDLINE (1966-September 2011) and EMBASE (1973-September 2011) was conducted using the search terms nitroglycerin, bone mineral density, fracture, and osteoporosis. References of identified articles were reviewed for additional citations.
All English-language articles related to the use of nitroglycerin ointment in postmenopausal women were reviewed.
Four observational studies reported significant improvements in bone mineral density of postmenopausal women with the use of nitrates. One pilot study and 2 prospective, randomized, placebo-controlled clinical trials reported conflicting results regarding the efficacy of nitroglycerin ointment.
Clinical data do not support use of nitroglycerin for this indication; its potential is limited at this time by inconclusive efficacy and a high incidence of headache. Further well-designed clinical trials demonstrating efficacy and safety of nitroglycerin ointment for prevention of postmenopausal osteoporosis are needed before this medication can be recommended for routine use.

Beckett RD, Sheehan AH
Ann Pharmacother Dec 2011
PMID: 22009995

Nitroglycerin Modestly Increases Bone Density and Decreased Resorption in Postmenopausal Women

Abstract

Effect of nitroglycerin ointment on bone density and strength in postmenopausal women: a randomized trial.

Nitroglycerin stimulates bone formation and inhibits bone resorption, is inexpensive, and is widely available. Its effects on bone density, bone structure, and bone strength are unknown. To determine if nitroglycerin increases lumbar spine bone mineral density (BMD) and to evaluate changes in hip BMD, bone geometry, and density at the radius and tibia, and markers of bone turnover.

A single-center, double-blind, placebo-controlled randomized trial conducted in Toronto, Ontario, Canada, for 24 months starting in November 2005 and completed in March 2010, of 243 postmenopausal women with lumbar spine T scores of between 0 and -2.0 who completed a 1-week run-in period taking nitroglycerin ointment. Intervention Nitroglycerin ointment (15 mg/d) or placebo applied at bedtime for 24 months.
Areal BMD at the lumbar spine, femoral neck, and total hip. Secondary outcomes included indices of bone geometry and strength at the distal radius and tibia, and biomarkers of bone formation (bone-specific alkaline phosphatase) and bone resorption (urine N -telopeptide).
At 2 years, women randomized to the nitroglycerin group had significant increases in areal BMD at the lumbar spine (from 1.05 to 1.14 g/cm(2) vs placebo from 1.06 to 1.08 g/cm(2); percentage change, 6.7%; 95% confidence interval [CI], 5.2%-8.2%; P < .001); total hip (from 0.92 to 0.97 g/cm(2) vs placebo from 0.93 to 0.92 g/cm(2); 6.2%; 95% CI, 5.6%-7.0%; P < .001); and femoral neck (from 0.88 to 0.93 g/cm(2) vs placebo from 0.87 to 0.86 g/cm(2); 7.0%; 95% CI, 5.5%-8.5%; P < .001). At 2 years, nitroglycerin also increased volumetric trabecular BMD (11.9% and 8.5%), cortical thickness (13.9% and 24.6%), periosteal circumference (7.4% and 2.9%), polar section modulus (10.7% and 9.8%), and polar moment of inertia (7.3% and 14.5%) at the radius and tibia, respectively (all P < .001); and increased bone-specific alkaline phosphatase by 34.8% and decreased urine N -telopeptide by 54.0% (P < .001). Incidence of serious adverse events did not differ between nitroglycerin (5 [4.2%]) and placebo (5 [4.3%]) groups. Among those women who continued treatment for 24 months, headaches were reported by 40 (35%) in nitroglycerin and 6 (5.4%) in placebo groups during the first month, decreasing substantially after 12 months.
Among postmenopausal women, nitroglycerin ointment modestly increased BMD and decreased bone resorption.

Jamal SA, Hamilton CJ, Eastell R, Cummings SR
JAMA Feb 2011
PMID: 21343579

There is a published comment on this study: Nitroglycerin needs more study.