JACN Did you know that you can get alerts when a new issue is online?
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Segal, E.
Right arrow Articles by Ish-Shalom, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Segal, E.
Right arrow Articles by Ish-Shalom, S.
Journal of the American College of Nutrition, Vol. 22, No. 3, 201-207 (2003)
Published by the American College of Nutrition

Original Research

Bone Density in Axial and Appendicular Skeleton in Patients with Lactose Intolerance: Influence of Calcium Intake and Vitamin D Status

Elena Segal, MD, Lubov Dvorkin, MD, Alexandra Lavy, MD, Geila S. Rozen, RD, PhD, Irit Yaniv, MD, Batia Raz, MSc, Ada Tamir, PhD and Sophia Ish-Shalom, MD

Metabolic Bone Diseases Unit (E.S., S.I.-S.), ISRAEL
Endocrine Laboratory, (B.R.), ISRAEL
Department of Clinical Nutrition (G.S.R.), ISRAEL
Rambam Medical Center, Gastroenterology Unit, Bnei Zion Medical Center (A.L.), ISRAEL
Department of Community Medicine and Epidemiology, Carmel Medical Center (A.T.), ISRAEL
The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology (A.T., S.I.-S.), ISRAEL
Haifa, Sunligth Ltd., Rehovot, (I.Y.), ISRAEL
Geriatric Department, Western Galilee Hospital, Naharyia (L.D.), ISRAEL

Address correspondence to: Sophia Ish-Shalom, M.D., Metabolic Bone Diseases Unit, Rambam Medical Center, P.O.B. 9602, 31096 Haifa, ISRAEL. E-mail: s_ish_shalom{at}rambam.health.gov.il


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 CONCLUSION
 REFERENCES
 
Background: Lactose intolerance (LI) is a common enzymatic insufficiency, manifesting by poor tolerance of dairy products, leading to low calcium intake and poor calcium absorption from dairy products. These changes might lead to an impairment of bone metabolism [1].

Objectives: To evaluate the impact of LI on quantitative bone parameters in axial and appendicular skeletal sites. To assess the impact of calcium intake from dairy and non-dairy nutritional sources, calcium regulating hormones and bone turnover on quantitative bone parameters in LI patients.

Methods: We evaluated calcium intake and bone status in sixty-six patients with LI, 49 women and 17 men, aged 20 to 78. Bone mass was assessed at the lumbar spine (LS), total hip (TH) and femoral neck (FN) by dual-energy x-ray absorptiometry (DEXA) and at the radius, tibia, phalanx by quantitative ultrasound. Serum calcium, albumin, inorganic phosphate, calcium regulating hormones and markers of bone turnover were evaluated.

Results: Total daily calcium intake was below the recommended by the American Dietetic Association [2] in all study participants (mean 692 mg/day ± 162). Elevated level of urinary deoxypyridinoline crosslinks (DPD) was observed in 63 (96%) patients and was negatively correlated with total daily calcium intake (r = -0.998, p = 0.025) and with nondairy calcium intake (r = -0.34, p = 0.015). Parathyroid hormone (PTH) level in the upper third of normal range (45–65 ng/L) was observed in 11 (17%) patients. Parathyroid hormone (PTH) was inversely correlated with total calcium intake (r = -0.4, p = 0.001), dairy calcium intake (r = -0.83, p = 0.05), non-dairy calcium intake (r = -0.29, p = 0.043), 25OHD3 serum level (r = -0.3, p = 0.007) and positively correlated with bone turnover markers (deoxypyridinoline crosslinks [DPD], r = 0.36, p = 0.01 and bone specific alkaline phosphatase [BSAP] r = 0.36, p = 0.01). Decrease in quantitative bone parameters compared to age-matched controls was observed in the axial and in the appendicular skeleton in men and in postmenopausal women: mean z-score for LS -0.87 ± 0.22 and -1.32 ± 0.65, p = 0.004 and 0.015, tibia -1.15 ± 0.53 and -0.44 ± 0.044, p < 0.001 and 0.27, phalanx -0.98 ± 0.22 and -0.52 ± 0.98, p < 0.001. We observed decrease in bone mass in patients with serum PTH in the upper tertile of normal range in the FN (z-score -0.57 ± 0.6 versus -0.03 ± 0.9, p = 0.025), TH (-0.51 ± 0.96 versus 0.04 ± 0.9, p = 0.05) and radius (-1.84 ± 0.27 versus -0.07 ± 1.61, p = 0.025, respectively). z-scores in FN and TH positively correlated with serum 25OHD3 level (r = 0.31, 0.29; p = 0.014, 0.019). In postmenopausal women serum 25OHD3 level correlated also with LS z-scores (r = 0.52, p = 0.004); FN and TH z-scores negatively correlated with DPD level (r = -0.51, p = 0.02 and r = -0.55, p = 0.04).

Conclusion: LI state may lead to increased bone turnover and decreased bone mass especially in men and postmenopausal women. Impaired vitamin D status and low calcium intake may be deleterious to bone in this condition.

Key words: lactase deficiency, bone density, calcium intake


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 CONCLUSION
 REFERENCES
 
Lactase deficiency (LD) affects approximately 15% of the white adults [3], but its prevalence varies widely between different countries and races, reaching 70% in the population of the Mediterranean Sea area [4]. The significant results of LD are low calcium intake and poor calcium absorption from dairy products, which may be contributing factors in the development of osteoporosis in LD patients.

Dietary calcium is important for normal bone metabolism. Some randomized trials have clearly demonstrated that calcium supplementation reduces the rate of bone loss in postmenopausal women [5]. Moreover, it has been shown that high calcium intake may decrease the frequency of osteoporotic fractures [6].

Patients with lactose intolerance, symptomatic LD, tend to reduce their intake of dairy products, which are the main source of calcium in the diet. Therefore, their calcium intake is low, and it might impair bone metabolism and bone strength, especially in weight bearing bones [7].

However, there are some controversial reports about influence of LD state on bone metabolism. It has been shown in several studies that patients with low lactase activity absorb calcium from lactose-containing products better than patients with normal lactase activity. A possible explanation might be that reduced calcium intake, caused by low calcium diet, results in a compensatory increase in calcium absorption [8–10].

Furthermore, it is not clear in which way low calcium diet influences the bone metabolism in young patients with LI.

The aim of this study was to evaluate calcium intake in different age groups of patients with LI, assess bone metabolism, bone parameters (i.e., density by DEXA and speed of sound [SOS] by QUS) in the appendicular and axial skeletal sites and their relationship with daily calcium intake from different dietary sources in patients with LI and to test the hypothesis that long term low calcium intake impairs bone metabolism in all age groups.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 CONCLUSION
 REFERENCES
 
Patients
Seventy-eight consecutive patients 20 to 78 years of age, with clinical signs of LI, were enrolled in the study during a six-month period. The patients were initially referred to Gastroenterology by primary care physicians for assessment of possible lactose intolerance due to clinical signs and symptoms of this condition. The diagnosis was confirmed in all patients by positive breath test. Forty-four patients were referred from the Department of Gastroenterology of Rambam Medical Center (Haifa), and 34 patients were recruited from the Gastroenterology Unit of Bnei Zion Medical Center. All patients provided informed consent to the study. Twelve patients were excluded from the study: one patient was diagnosed with osteogenesis imperfecta; two, with chronic renal failure; one, with hypocalciuric hypercalcemia; two, due to history of recent malignancy. Six patients did not complete the diagnostic evaluation. Thus, 66 patients, 49 women (18 premenopausal, 31 postmenopausal) and 17 men were included in the study. Clinical assessment included detailed medical history, with special attention to information about duration of signs and symptoms of LI, fracture history and physical examination.

Lactase Deficiency Diagnosis
LD was diagnosed following characteristic clinical signs and symptoms and was confirmed by positive H2 breath test performed after a 12-hour fasting period using a commercial device, EC 60 Breath Hydrogen Monitor (Bedfont Scientific, Ltd, England). Smoking and physical exercise were not allowed one hour before and through the test. The patients were instructed to avoid deep inspiration and not to hyperventilate before exhalation. Breath samples were taken at fasting (baseline) and every 30 minutes for a four-hour period, after consumption of 50 g of lactose in 100 mL of water. The test was considered as indicative for LD when the concentration of H2 in the expired air increased by more than 20 parts per million (ppm) above baseline [11].

Dietary Evaluation
Calcium intake from different sources was evaluated in each patient using a semi-quantitative food frequency questionnaire adapted, with permission from W. Willet [12], by the Department of Clinical Nutrition, Rambam Medical Center [13].

Laboratory Evaluation
The intact PTH level was assessed by immunoradiometric assay (Nichols Institute Diagnostics, San Juan Capistrano, CA), 25[OH]D3 by 125I-radioimmunoassay (DiaSorin, Stillwater, MN), 1,25[OH]2D3 by 3H-radioreceptor assay (DiaSorin, Stillwater, MN), BSAP by immunoradiometric assay (Tandem-R-Ostase, Beckman Coulter, Fullerton, CA), DPD by Pyrilinks-D ELISA (Metra Biosystems, Mountain View, CA). Calcium and inorganic phosphate concentration in serum, serum levels of creatinine, albumin, liver enzymes and TSH, as well as calcium excretion in 24-hour urine collection, were performed using standard laboratory techniques (Hitachi 747, Roche).

Bone Mass Measurement
Bone was assessed by two technologies: bone mineral density (BMD) and SOS. BMD of the spine (L2–L4), total hip and at the femoral neck was measured using a Lunar DPX scanner (Madison, WI).

BMD of the peripheral skeleton was evaluated using the Quantitative Ultrasound Measurement (Omnisense prototype, Sunlight Ltd, Israel) by defining SOS in the distal 1/3 radius (RAD) of non-dominant hand, midshaft tibia (TIB), proximal phalanx III (PHAL), metatarsal V (MET).

Statistical Analysis
A one-way ANOVA was used to test the differences of calcium intake between men, premenopausal and postmenopausal women. The mean and standard deviation (SD) of laboratory tests were calculated with the percent of patients below and above normal. Pearson correlation coefficient was used to assess the relationship between the continuous variables. Student’s t test was used to compare the mean values of different variables in the patients’ subgroups. Partial correlation was used to adjust for effects of age and gender. The mean and SD of PTH and DPD levels were calculated for the different dairy and total calcium intake groups. The correlation between SOS, BMD, serum tests and calcium intake were evaluated using non-parametric (Spearman’s) correlation.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
CONCLUSION
 REFERENCES
 
Patients’ Characteristics
Duration of LI state was between six months to 20 years, according to patients’ medical history. All patients demonstrated typical clinical signs of LI after consumption of 50 g of lactose: 15 (23%) patients during 30 minutes, 34 (52%) patients during one hour and 17 (26%) patients during one and a half to two hours. We observed rise of H2 value >20 ppm above baseline in expired air in the mean time frame of one hour (minimal time was 30 minutes, maximal time was two hours). Six patients in the observed group were smokers: two postmenopausal women and four men. Seven postmenopausal women were diagnosed as osteoporotic before the study, but none of the postmenopausal women received any therapy and/or calcium supplements. Six women (12% of all women) reported three wrist fractures and four ankle fractures, and one man (6% of all men) reported a hip fracture. All patients sustained fractures before the age 50; all fractures were reported as traumatic.

Evaluation of Calcium Intake
Daily calcium intake (Table 1) was 300–900 mg/day, mean 692 ± 162. Non-dairy calcium sources were sardines, green leafy vegetables and soybeans. Total daily calcium intake was <500 mg/day in 13 (20%) patients and 500–1000 mg/day in 43 (65%) patients, and only 10 (15%) patients had >1000 mg/day calcium in their regular diet. The lowest total Ca intake was found in the men. There was no statistical significance between subgroups regarding diary, non-diary and total calcium intake.


View this table:
[in this window]
[in a new window]
  		Table 1. Daily Calcium Intake (mg) from Different Sources (mean ± SD) in Lactase Deficiency Patients

 
Laboratory Evaluation
Two patients (3%) had serum PTH level >65 ng/L (normal 10–65 ng/L); in 11 (17%) patients serum PTH level was in the upper third of the normal range (45–65 ng/L). Total calcium intake negatively correlated with PTH (r = -0.4, p = 0.001). Dairy calcium intake inversely correlated with PTH, using univariant correlation (r = -0.86, p < 0.09) (Fig. 1) and with nondairy calcium intake (r = -0.3, p = 0.042), using partial correlation analysis.



View larger version (16K):
[in this window]
[in a new window]
  		Fig. 1. Parathyroid hormone (PTH) level and dairy calcium intake in LI patients.

 
Fourteen patients (21%) had low 25[OH]D3 serum level. Three (5%) of them had serum level of 25[OH]D3 <10 ng/mL and were diagnosed with vitamin D deficiency. Vitamin D insufficiency was observed in 11 patients (17%) who had 25[OH]D3 serum level 10–15 ng/mL.

Serum PTH and 25[OH]D3 levels were negatively correlated (r = -0.695, p = 0.03). The correlation remained significant after adjustment for age: r = -0.3, p = 0.007. Positive correlation after adjustment for age was observed between PTH and bone turnover markers (deoxypyridinoline [DPD], r = 0.36, p = 0.01, and bone specific alkaline phosphatase [BSAP], r = 0.35, p = 0.01). In men PTH correlated significantly with DPD (r = 0.5, p = 0.045), in premenopausal women correlation between PTH and BSAP was observed (r = 0.6, p = 0.01).

High level of DPD was observed in 63 (96%) patients, while BSAP was increased in 8 (12%) patients (Table 2). Inverse correlation between calcium intake and DPD was observed (r = -0.998, p = 0.025) (Fig. 2). Hypocalciuria (urinary calcium excretion <100 mg/24hours) was observed in 32 (49%) patients.


View this table:
[in this window]
[in a new window]
  		Table 2. Bone Markers in Patients with Lactase Deficiency

 


View larger version (40K):
[in this window]
[in a new window]
  		Fig. 2. Deoxypyridinoline (DPD) level and total calcium intake in LI patients.

 
Routine laboratory tests were within normal range for adults in all patients.

BMD Evaluation
Decreased BMD results in different measurement sites were observed in all study groups: premenopausal and postmenopausal women and in men (Table 3). z-scores in FN and TH positively correlated after correction for age with serum 25OHD3 level, r = 0.31, p = 0.014 and r = 0.29, p = 0.019. In postmenopausal women serum 25OHD3 level correlated also with LS z-scores (r = 0.52, p = 0.004). In this group FN and TH z-scores negatively correlated with DPD level, r = -0.51, p = 0.02 and r = -0.55, p = 0.04.


View this table:
[in this window]
[in a new window]
  		Table 3. Bone Mineral Density z-Scores (Mean ± SD) in Lactase Deficiency Patients

 
Comparison of SOS measurement results of study population to healthy people is illustrated on Fig. 3. Patients with serum PTH level >45 ng/L had a statistically significant decrease in femoral neck and total hip BMD z-scores compared to those with lower serum PTH level (mean z-score -0.57 ± 0.6 versus -0.03 ± 0.9, p = 0.025 and -0.51 ± 0.96 versus 0.04 ± 0.9, p = 0.05, respectively), as well as in radius SOS (-1.84 ± 0.27 versus -0.07 ± 1.61, p = 0.025). Patients with 25[OH]D3 level <15 ng/mL had significantly lower femoral neck BMD z-scores (-0.42 ± 0.62 versus -0.02 ± 0.9, p = 0.05). There was no correlation found between BMD and body mass index (BMI); SOS in tibia positively correlated with BMI (r = -0.46, p < 0.0001), for the whole group.



View larger version (40K):
[in this window]
[in a new window]
  		Fig. 3. Bone parameters in lactose intolerance (LI) patients, measured by ultrasound (in units of speed of sound [SOS]).

 
Using different statistical analyses, we did not observed dependence of BMD changes from duration of LI state. Most of the patients could not state the exact time point of the initiation of the LI symptoms on repeated questioning, which posed a difficulty in establishing valid correlation between disease duration and measurable variables.


   DISCUSSION
 
The contribution of LD to the development of osteoporosis is not distinct. In the last 30 years several different opinions have been suggested in the literature. In 1967 Birge proposed that LD promotes a decrease in BMD [14]. Later studies were published, evidencing that among LD patients there are more osteoporotic patients than among an analogous group of healthy persons [15,16]. Honkanen observed lower BMD in weight bearing bones in postmenopausal patients with LI.[17].

The low calcium intake, by avoidance of dairy products, but not the LI state by itself was found to have negative influence on BMD parameters [18–20]. Honkanen [7] found a decrease in femoral neck BMD in perimenopausal women with LI, also possibly due to reduced calcium intake. We evaluated bone metabolism and bone parameters in the appendicular and axial skeletal sites in symptomatic patients with confirmed LD by H2 breath test that could be defined as lactase intolerant. In the given group of patients with LI, we observed a decrease in daily calcium intake in comparison with the recommended daily intake (RDI) (1000 to 1200 mg/day) [2], mainly due to decreased intake of dairy products. In most Western countries more than two-thirds of the dietary calcium intake is derived from milk and diary products [21,22]. In our group diary calcium intake was much lower: 16% to 19% of RDI in men, 24% to 29% in premenopausal women and 21% to 25% in postmenopausal women. However, patients in the observed group consumed different amounts of dairy products, which can be explained by a difference in the severity of LD: from absence of the enzyme in the intestine to an amount that permits an intake of certain dairy products that have undergone fermentation (yogurt, clotted milk, cheese, etc.). We observed some changes in serum PTH level, which might be induced by decreased total and dairy calcium intake. Serum PTH level was negatively correlated with total calcium intake. It also has a trend to increase in patients with the lowest daily calcium intake compared to the patients with moderate calcium intake. Increase in serum PTH may lead to decreased urinary calcium excretion, increased bone turnover and consequent decrease in bone mass.

Twenty one percent of our patients had impaired 25[OH]D3 serum level. Strong positive correlation between 25[OH]D3 level and BMD z-scores in FN and TH stressed the importance of vitamin D status for bone health, especially in postmenopausal LI patients. A decrease in calcium intake and impaired calcium absorption from dairy products in the small intestine are the main reasons for a negative calcium balance. This brings an acceleration of bone turnover and an impairment of bone metabolism in trabecular as well as in cortical bones [16,23]. Pietschmann [24] reported increased osteocalcin levels in LD patients. We observed an increase in bone turnover, mainly in the bone resorption phase in the majority of our patients. A strong inverse correlation between urinary DPD level and daily calcium intake deserves special attention. In the postmenopausal women, an increase in bone resorption marker levels can be explained by the estrogen deficit. However, in the postmenopausal women subgroup, the BMD values adjusted for age (z-scores) were lower than the average rates. This might indicate an additive effect of lactose intolerance and estrogen deficit on bone metabolism in postmenopausal women. Decrease in bone mass in the lumbar spine, as well as in the peripheral skeleton, might be an outcome of an accelerated bone turnover due to decreased calcium intake. Bone turnover is an independent factor that predicts bone fractures due to its influence on bone microstructure [25]. It was shown that bone fractures might occur without significant decrease in BMD, but only due to changes of the bone microstructure [26,27]. In this light, the LD state seems to be extremely important, especially in the young who demonstrate impairment in bone metabolism in this condition. Decrease in bone mass in the lumbar spine and in the peripheral skeleton, which we observed in our patients, might reflect an accelerated bone turnover due to decreased calcium intake. Negative correlation observed between FN BMD and PTH level deserves special attention in risk assessment for future hip fracture. The negative correlation between DPD and FN and TH z-scores that we observed in postmenopausal women might reflect the future fracture risk.

In all our patients dairy calcium intake did not exceed 26%. This may negatively affect bone metabolism during achievement of peak bone mass at a young age and its maintenance in adulthood [19]. The risk of osteopenia was increased in children with an intake of dairy calcium lower than 60% of total recommended daily allowance [28]. The positive effect of estrogen in the premenopausal women may partly compensate for this impairment. Subsequently, BMD values were higher in this group, but still lower than in the age-matched healthy population. Therefore, decrease of bone mass in LI patients should be diagnosed and corrected by proper diet or pharmacological supplements in all age groups, because anti-resorptive therapy initiated later in the life or later in the disease process may be less effective in reducing fracture rates [19,29,30]. Studies during the last ten years have shown that yogurt is well tolerated by lactose intolerant persons, in spite of same lactase content. The presence of living lactic acid bacteria in fermented dairy products make them tolerable to lactose intolerant persons, and these products should be considered an important source of calcium [31]. Sufficient calcium intake might be important for optimal response to bone active agents—estrogen SERMS and bisphosphonates [32].


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 CONCLUSION
REFERENCES
 
Low calcium intake due to LI might influence bone metabolism independently from age and gender and may lead to a decrease in bone mass in the axial and in the appendicular skeleton following increases in bone turnover markers and serum PTH level. Impaired vitamin D status may further contribute to a decrease in bone mass. The early diagnosis of LD and dietary correction of low calcium intake and vitamin D status might be important for prevention of impairment in bone metabolism and early development of osteoporosis.

Received July 24, 2002. Accepted January 3, 2003.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 CONCLUSION
 REFERENCES
 

  1. Lee MF, Krasinski SD: Human adult-onset lactase decline: an update. Nutr Rev56 :1 –8,1998 .[Medline]
  2. Yates AA, Sandra A, Schlicker SA, Suitor CW: Dietary reference intakes: the new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc98 :699 –706,1998 .[Medline]
  3. Slemenda CW, Christian JC, Hui S, Fitzgerald J, Conrad-Johnston C: No evidence for an effect of lactase deficiency on bone mass in pre- or postmenopausal women. J Bone Miner Res6 :1367 –1371,1991 .[Medline]
  4. Gudmand-Hoyer E: The clinical significance of disaccharide maldigestion. Am J Clin Nutr59(3 Suppl) :735S –741S,1994 .[Abstract/Free Full Text]
  5. Horowitz M, Wishart J, Mundy L, Nordin B: Lactose and calcium absorption in postmenopausal osteoporosis. Arch Intern Med147 :534 –536,1987 .[Abstract]
  6. Scopacasa F, Horowitz M, Wishart JM, Need AG, Morris HA, Wittert G, Nordin BEC: Calcium supplementation suppresses bone resorption in early postmenopausal women. Calcif Tissue Int62 :8 –12,1998 .[Medline]
  7. Honkanen R, Pulkkinen P, Jarvinen R, Kroger H, Lindstedt K, Tuppurainen M, Uusitupa M: Does lactose intolerance predispose to low bone density? A population-based study of perimenopausal Finnish women. Bone19 :23 –28,1996 .[Medline]
  8. Holbrook TL, Barret-Connor E, Wingard DL: Dietary calcium and risk of hip fracture: 14-year prospective population study. Lancet2(8619) :1046 –1049,1988 .[Medline]
  9. Cochet B, Jung A, Griessen M, Bartholdi P, Schaller P, Donath A: Effects of lactose on intestinal calcium absorption in normal and lactase deficient subjects. Gastroenterology84 :935 –940,1983 .[Medline]
  10. Duncombe VM, Watts RWE, Peters TJ: In vitro calcium uptake by jejunal biopsy specimens from patients with idiopathic hypercalciuria. Lancet2(8208–8209) :1334 –1336,1980 .[Medline]
  11. Metz G, Jenkins DJ, Peters TJ, Newman A, Blendis LM: Breath hydrogen as a diagnostic method for hypolactasia. Lancet1(7917) :1155 –1157,1975 .[Medline]
  12. Willett W: "Nutritional Epidemiology," 2nd ed. New York: Oxford University Press, pp74 –100,1998 .
  13. Rozen GS, Rennert G, Rennert HS, Diab G, Diab D, Ish-Shalom S: Calcium intake and bone mass development among Israeli adolescent girls. J Am Coll Nutr20 :219 –224,2001 .[Abstract/Free Full Text]
  14. Birge SJ, Keutmann HT, Cautrecasas P, Whedon GD: Osteoporosis, intestinal lactase deficiency and low dietary calcium intake. N Engl J Med8 :445 –447,1967 .
  15. Newcomer AD, Hodgson SF, McGill DB, Thomas PJ: Lactase deficiency: prevalence in osteoporosis. Ann Intern Med89 :218 –220,1978 .
  16. Murphy S, Khaw K, May H, Compston JE: Milk consumption and bone mineral density in middle aged and elderly women. BMJ308 :939 –942,1994 .[Abstract/Free Full Text]
  17. Honkanen R, Kroger H, Alhava E, Turpeinen P, Tuppurainen M, Saarikoski S: Lactose intolerance associated with fractures of weight-bearing bones in Finnish women aged 38–57 years. Bone21 :473 –477,1997 .[Medline]
  18. Corazza GR, Benati G, Di Sario A, Tarozzi C, Strocchi A, Passri M, Gasbarrini G: Lactose intolerance and bone mass in postmenopausal Italian women. Br J Nutr73 :479 –487,1995 .[Medline]
  19. Di Stefano M, Veneto G, Malservisi S, Cecchetti L, Minguzzi L, Strocchi A, Corazza GR: Lactose malabsorption and intolerance and peak bone mass. Gastroenterology122 :1793 –1799,2002 .[Medline]
  20. Goulding A, Taylor RW, Keil D, Gold E, Lewis-Barned NJ, Williams SM: Lactose malabsorption and rate of bone loss in older women. Age Ageing28 :175 –1780,1999 .[Abstract/Free Full Text]
  21. Black RE, Williams SM, Jones IE, Goulding A: Children who avoid drinking cow milk have low dietary calcium intakes and pure health. Am J Clin Nutr76 :675 –680,2002 .[Abstract/Free Full Text]
  22. Weaver CM: Calcium requirements of physically active people. Am J Clin Nutr72 :S579 –S584,2000 .[Abstract/Free Full Text]
  23. Baran D, Sorensen A, Grimes J, Lew R, Karellas A, Johnson B, Roche J: Dietary modification with dairy products for preventing vertebral bone loss in premenopausal women: a three-year prospective study. JCEM70 :264 –269,1990 .[Abstract]
  24. Pietschmann P, Knoflach P, Wolosczczuk W: Increased serum osteocalcin in patients with lactase deficiency. Am J Gastroenterol86 :72 –74,1991 .[Medline]
  25. Miller PD, Baran DT, Bilezikian JP, Greenspan SL, Lindsay R, Riggs BL, Watts NB: Practical clinical application of biochemical markers of bone turnover. J Clin Densitom2 :323 –342,1999 .[Medline]
  26. Rosen CJ, Tenenhouse A: Biochemical markers of bone turnover. A look at laboratory tests that reflect bone status. Postgrad Med104 :101 –102,107–110,113–114,1998 .
  27. Manolagas SC, Jilka RL: Bone marrow, cytokines, and bone remodeling: emerging insights into the pathophysiology of osteoporosis: N Engl J Med332 :305 –311,1995 .[Free Full Text]
  28. Infante D, Tormo R: Risk of inadequate bone mineralization in diseases involving long-term suppression of dairy products. J Pediatr Gastroenterol Nutr30 :310 –313,2000 .[Medline]
  29. Resnik NM, Greenspan SL: Senile osteoporosis reconsidered. JAMA261 :1025 –1029,1989 .[Abstract]
  30. Sambrook PN: The treatment of postmenopausal osteoporosis. N Engl J Med333 :1495 –1496,1995 .[Free Full Text]
  31. Sieber R, Stransky M, de Vrese M: lactose intolerance and consumption of milk and milk products. Z Ernahrugswiss36 :375 –393,1997 .[Medline]
  32. Heaney RP: Constructive interactions among nutrients and bone—active pharmacologic agents with principal emphasis on calcium, phosphorus, vitamin D and protein. J Am Coll Nutr20 :S403 –S409, S417–S420,2001 .[Abstract/Free Full Text]
  33. Miller PD, Baran DT, Bilezikian JP, Greenspan SL, Lindsay R, Riggs BL, Watts NB: Practical clinical application of biochemical markers of bone turnover. J Clin Densitom2 :323 –342,1999 .



This article has been cited by other articles:


Home page
 J. Am. Coll. Nutr.Home page
H. Y. Lovelace and S. I. Barr
Diagnosis, Symptoms, and Calcium Intakes of Individuals with Self-Reported Lactose Intolerance
J. Am. Coll. Nutr., February 1, 2005; 24(1): 51 - 57.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Segal, E.
Right arrow Articles by Ish-Shalom, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Segal, E.
Right arrow Articles by Ish-Shalom, S.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS