Bone health status of premenopausal healthy adult females in Pakistani females

ORIGINAL ARTICLE

Bone health status of premenopausal healthy adult femalesin Pakistani females

Farhan Javed Dar & Romaina Iqbal & Farooq Ghani &Imran Siddiqui & Aysha Habib Khan

Received: 24 April 2012 /Accepted: 4 May 2012 /Published online: 26 May 2012# International Osteoporosis Foundation and National Osteoporosis Foundation 2012

AbstractSummary Bone health status in healthy premenopausalfemales was assessed. We found high bone turnover in36.8 % and vitamin D deficiency and insufficiency in 82.8and 16.1 %, respectively, and secondary hyperparathyroid-ism in 25.9 % of the subjects. This is alarming as there isinability to achieve peak bone mass and predisposes toosteoporosis risk.Purpose This study aimed to assess bone health status inhealthy females by using biochemical markers of bonemetabolism in blood [N-telopeptide of type I collagen(NTx), 25-hydroxyvitamin D (25OHD), and plasma intactparathyroid hormone (iPTH)].

Material and methods One hundred and seventy-four healthypremenopausal female volunteers were recruited from an ur-ban residential area in Karachi. Demographic details werecollected on a preformed questionnaire. Blood samples forthe estimation of serum NTx, 25OHD, and plasma iPTH weretaken in a fasting state. Data were analyzed using StatisticalPackage for Social Sciences 16.0. A p value of <0.05 wasconsidered as significant.Results High bone turnover, as depicted by NTx, was seenin 36.8 % cases. Vitamin D deficiency, insufficiency, andsufficiency were seen in 82.8, 16.1, and 1.1 % respectively.Secondary hyperparathyroidism was present in 25.9 % ofthe subjects, while others had blunted PTH response.Significant correlates of bone health were serum 25OHDlevels, duration of sun exposure, and the practice of wearingveil (p value<0.001).Conclusion Bone turnover is high with high prevalence ofvitamin D deficiency in apparently healthy premenopausalfemales predisposing them to higher risk for development ofosteoporosis.

Keywords Bone . Health . Cross-linked N-telopeptide oftype I collagen (NTx) . Premenopausal . Vitamin Ddeficiency . Secondary hyperparathyroidism . Pakistan

Introduction

It is essential to build good quality bone in childhood and teenyears and maintain bone health with adequate nutrition andlifestyle to avoid bone-related problems, like osteoporosis inlater life. To date, the role of calcium and vitamin D as themajor determinants of bone health is well established, and thedeficiency has adverse consequences for the skeleton [1].Vitamin D deficiency [25-hydroxyvitamin D (25OHD),

F. J. Dar : F. Ghani : I. Siddiqui :A. H. KhanDepartment of Pathology & Microbiology, Aga Khan University,Stadium Road, Karachi, Pakistan

F. J. Dare-mail: [email protected]

F. Ghanie-mail: [email protected]

I. Siddiquee-mail: [email protected]

R. IqbalDepartment of Community Health Sciences and Medicine,Aga Khan University,Stadium Road, Karachi, Pakistane-mail: [email protected]

A. H. Khan (*)Department of Pathology & Microbiology and Medicine,Aga Khan University,Stadium Road, Karachi, Pakistane-mail: [email protected]

Arch Osteoporos (2012) 7:93–99DOI 10.1007/s11657-012-0085-0

VDD] prevents the buildup of the maximum amount of calci-um that is genetically preprogrammed for the skeleton, resultsin secondary hyperparathyroidism (sHPTH), and increasesbone resorption, thereby reducing the amount of peak bonemass achieved [2]. This produces osteopenia, osteoporosis,and fragility fractures after menopause. There has been anincrease in the use of bone turnover marker (BTM) to assessbone remodeling status and for monitoring the response toosteoporosis treatment. Imbalances in bone remodeling due tovarious grades of VDD have been illustrated previously usingBTMs [3]. High frequency of VDD has been reported fromPakistan in apparently healthy adult females [4, 5], but there isscarcity of data on the magnitude of the problem from withinPakistan. Therefore, we conducted this preliminary study toassess bone health as measured by BTM: serum N-telopeptideof type I collagen (NTx), 25OHD, and plasma intact parathy-roid hormone (iPTH) in ambulatory and apparently healthyadult premenopausal females residing in Karachi, Pakistan.

Material and methods

Methodology

An analytical, cross-sectional study was carried out fromNovember 2007 to June 2008. Apparently healthy adultfemales aged ≥18 years were interviewed and recruitedthrough convenient, nonpurposive sampling. Subjects wererecruited in a community-based door to door survey con-ducted in District East of Karachi. We selected UnionCouncil Jamshed Town randomly for participant recruit-ment. Females with no active disease were stated “appar-ently healthy.” Females taking vitamin D or calciumsupplements or any medicine such as hormone replacementtherapy and oral contraceptives were not recruited in thestudy. The study was approved by Ethical ReviewCommittee (ERC), standing committee of the UniversityResearch Council (URC), of the Aga Khan University(811-Pat/ERC-07).

Data collection procedure

Information regarding the participant's name, age, weight,height, ethnicity, exercising habits, duration of sun expo-sure, and veil status were gathered by the primary investi-gator in a predesigned questionnaire. Standing height wasmeasured using a fixed scale, and weight was taken on astandard floor scale in light clothing.

Blood sampling and storage

Eight milliliter of blood was withdrawn from the antecubitalvein in a fasting state (8 h fasting) for biochemical analysis.

All blood samples were centrifuged. Serum and plasmastored at −70°C until assayed.

Biochemical analysis

Bone turnover was assessed by measuring NTx using anELISA kit Osteomark NTx from Ostex International, Inc.,Seattle, WA. For quality control, low and high controls wererun. Inter-assay and intra-assay variability for the serumNTx assays were 6.9 and 4.6 %, respectively. Results wereexpressed as nanomoles of bone collagen equivalents perliter of serum (nMBCE/L). The ranges of the serum NTxlevels in healthy females were taken 6.2–19.0 nMBCE/Lwith a mean of 12.6 nMBCE/L. Serum NTx level >19nMBCE/L was taken as high bone turnover.

Vitamin D status was determined by measuring serum25OHD3 concentrations by electrochemiluminescence im-munoassay on Elecsys autoanalyzer (Roche Diagnostics).For quality control low, medium and high ElecsysPreciControls were used. The within-run CVs were 5.7,5.7, and 5.4 % at concentrations of 25.2, 39.9, and65.6 ng/ml. 25OHD3 blood levels were taken as: >30 ng/ml as sufficient; 21–29 ng/ml as insufficient; and <20 ng/mlas deficient.

Plasma iPTH level was measured by Immulite(Diagnostic Products Corporation, Los Angeles, CA,USA). For quality control, two levels (normal and high)were used. The assay has an intra-assay precision of5.5 %, an inter-assay precision of 7.9 %, and the referencerange is 16–87 pg/ml.

Data analysis procedure

Data was presented as mean ± SD. Descriptive statistics forage groups, body mass index (BMI) status, ethnicity, exer-cising habits, duration of sun exposure, veil status, boneturnover status (NTx status), 25OHD status, and iPTH statuswere computed.

The mean of biochemical tests (NTx, 25OHD, and iPTH)were computed by age groups, BMI status, ethnicity, exer-cising habit, sunlight exposure, and veil status of females.Histograms were made to see the normal distribution. TheNTx and iPTH levels had to be logarithmically transformedin order to normalize their distribution, and the logarithmiclevels were used for further analysis [log-transformed NTx(LN NTx) and log-transformed iPTH (LN iPTH)].Univariate and multiple linear regressions were conductedusing serum NTx as the independent variable and serum25OHD, LN iPTH, BMI, ethnicity, exercising habits, andduration of sun exposure as dependent variables. A p valueof <0.05 was treated as significant in all above statisticalanalyses. The Statistical Package for Social Sciences 16.0was used for data analysis.

94 Arch Osteoporos (2012) 7:93–99

Results

Demographic details and biochemical data of two hundredhealthy female adults were collected. Out of which, 174females (87 %) aged between 18–48 years (mean 29.06±6.89) were premenopausal and included in the final analysis.The mean blood NTx was 18.85±8.56 nMBCE/L, 25OHDwas 15.32±6.16 ng/ml, and iPTH was 73.35 pg/ml.

The subjects were distributed into two age groups (belowor above 30 years) according to peak bone mass attainmentage. A total of 107 (61.5 %) were below 30 years of age and67 (38.5 %) were above 30 years of age. Body mass index,categorized by South Asian BMI classification showed 25(14.4 %), 68 (39.1 %), 29 (16.7 %), and 52 (29.9 %) to beunderweight, healthy weight, overweight, and obese, re-spectively. These numbers highlight that roughly one inthree females are obese in our population. Major ethnicgroup is Urdu speaking (95, 54.6 %) then Punjabi (27,15.5 %), Sindhi (21, 12.1 %), Pathan (15, 8.6 %), and others(16, 9.2 %); Others included Balochi, Hunzai, and Memon.Most subjects (135, 77.6 %) did not do regular exercise.

The duration of sun exposure per week for subjectscomprised of varied interval: 39 (19.5 %) were exposedto <30 min, 114 (57 %) were exposed 30–60 min, and47 (23.5 %) were exposed <60 min. Veil practice wasobserved by 43 (21.5 %) females.

Assessment of biochemical parameters showed high se-rum NTx levels (>19 nMBCE/L) in 64 (36.8 %) females,while in 110 (63.2 %) females, the levels were within thereference range (6.2–19 nMBCE/L). One hundred forty-foursubjects (82.8 %) had deficient 25OHD (<20 ng/ml), 28(16.1 %) had insufficient 25OHD (21–29 ng/ml), and 2(1.1 %) had sufficient 25OHD. iPTH levels were raised(secondary hyperparathyroidism) in 45 (25.9 %), while129 (74.1 %) had iPTH levels within the reference range.

Mean blood levels of biochemical markers according tobone turnover, 25OHD, and iPTH status are reported inTable 1. Mean 25OHD levels were elevated in subjects with

high NTx (p value00.05) and lower in subjects with highiPTH (p value00.004). Mean NTx levels did not differamong 25OHD status (p value00.27) and iPTH status (pvalue00.5). Mean iPTH levels were high in VDD subjectsas compared to insufficient and sufficient state (p value00.01). Mean iPTH levels did not differ between NTx status(p value00.91).

The mean NTx levels did not differ among age groups:18.5 and 19.3 nMBCE/L in 18–30 years and 31–48 yearsfemales, respectively (p value00.5); BMI status, 18.2, 19.6,20.3, and 17.2 nMBCE/L in underweight, healthy weight,overweight, and obese females, respectively (p value00.32);ethnicity, 18.6, 18.4, 20.2, 15.1, and 22.4 nMBCE/L in Urduspeaking, Punjabi, Sindhi, Pathan, and others (Balochi,Hunzai, etc.), respectively (p value00.17); and exercisinghabits, 18.6 and 19.5 nMBCE/L in females not doing ordoing exercise, respectively (p value00.56). However, meanNTx values were high in females exposed to sun <30 minweekly (24.2 nMBCE/L) than females exposed >30 min tosun weekly (17.6 nMBCE/L, p value00.01), although themean NTx level was normal in subjects observing veil(16.2 nMBCE/L) compared to females not observing veilpractice (19.5 nMBCE/L, p value00.01).

Mean 25OHD level was deficient in both the age groupsbut high mean level was seen in females 31–48 years(16.56 ng/ml) compared to females 18–30 years of age(14.55 ng/ml, p value00.04) with mean iPTH levels of80.0 and 69.16 pg/ml respectively. While mean 25OHDlevels did not differ among BMI status (15.3, 15.4, 15.9,and 14.9 ng/ml in underweight, healthy weight, overweight,and obese females, respectively; p value00.91), the meaniPTH levels were significantly different (63.4, 68.2, 72.6,and 85.1 pg/ml in underweight, healthy weight, overweight,and obese females, respectively; p value00.03). In obesefemales, the mean iPTH levels (85.1 pg/ml) were high ascompared to others.

Mean 25OHD levels differ among different ethnicity(p value00.02) with the Pathans (11.4 ng/ml) more

Table 1 Mean blood levels ofNTx, 25OHD, and iPTH withrespect to biochemical status

Means with different letters arestatistically significant; for pvalue, refer to text

NTx 25OHD iPTH

NTx status

Normal turnover (6.2–19 nMBCE/L) n0110 (63.2 %) 13.9 a 14.6 a 73.5 a

High turnover (>19 nMBCE/L) n064 (36.8 %) 27.3 b 16.5 b 72.9 a

25OHD status

Sufficient (>30 ng/ml) n002 (1.1 %) 13.0 a 34.2 a 55.7 a

Insufficient (21–29 ng/ml) n028 (16.1 %) 20.8 a 24.5 b 56.2 a

Deficient (<20 ng/ml) n0144 (82.8 %) 18.5 a 13.2 c 76.9 b

iPTH status

Normal (16–87 pg/ml) n0129 (74.1 %) 18.5 a 16.0 a 55.9 a

High (>87 pg/ml) n045 (25.9 %) 19.6 a 13.3 b 123.3 b

Arch Osteoporos (2012) 7:93–99 95

severely deficient compared to others (p value00.04).The Pathans also had high iPTH levels (100.6 pg/ml)as compared to Urdu speaking (68.1 pg/ml, p value00.01).

The duration of sun exposure per week did not showany influence on 25OHD levels (15.6, 14.9, and 16.0 ng/mlin <30, 30–60, and >60min sun exposure weekly, respectively;p value00.6) and iPTH level (80.0, 70.2, and 76.1 pg/mlin <30, 30–60, and >60 min sun exposure weekly,respectively; p value00.36). Though subjects observingveil practices had low 25OHD levels (13.8 ng/ml) com-pared to females without veil (15.7 ng/ml; p value00.09), high iPTH levels (81.3 pg/ml) were seen infemales who wore veil as compared to females whodid not wear veil (71.1 pg/ml; p value00.19).

Determinants of bone turnover: NTx

We investigated the determinants of NTx levels in adultfemales. Log transformation was done to normalize thedistribution of serum NTx and plasma iPTH. On univariateregression analysis, age, BMI, ethnicity, and exercise didnot affect LN NTx (p value>0.05), though age and BMIwere kept in final model due to biological importance.LN iPTH was identified as confounders [>10 % changein unstandardized coefficient (25OHD)] and was alsokept for further analysis because of biological impor-tance of plausibility. Multiple linear regression analysiswas performed using LN NTx as independent variableand serum 25OHD, age, BMI, ethnicity, duration of sunexposure, and veil practice as dependent variables(Table 2). There was no significant association withiPTH levels. NTx levels were directly associated with25OHD levels (p value00.009), while duration of sunexposure and veil status were inversely associated, i.e.,subjects less exposed to sun (p value00.001) and didnot observe veil practice had high serum NTx levels(p value00.009).

Discussion

Raised mean serum NTx levels (18.8±8.5 nMBCE/L) wereseen in this study with high turnover in 36.8 % of healthysubjects in comparison with other populations such asChinese (13.72 nMBCE/L), Japanese (13.52 nMBCE/L),and Nigerians (16.2 nMBCE/L) [6–8]. This percentage isalarming as this is one of the mechanisms which leads toexcessive bone resorption and increased risk of osteoporosisin later life in addition to inability to achieve peak bonemass due to inadequate formation of new bone duringremodeling. Approximately 12 % of the total variation inNTx concentration was explained by the model shown inTable 2 (R00.388; R200.15; adjusted R200.114; p value<0.001). 25OHD was found as a major determinant of serumNTx accounting alone for 4 % of the total variation in NTxconcentration. Adami et al. recently reported a positiveassociation between bone turnover marker, serum CTx,and 25OHD in young premenopausal females [9] similarto the association observed in this study using serum NTx(Table 2). Serum NTx was not affected by iPTH and alsomean iPTH was similar in normal and high bone turnovergroups. This may be due to the direct impact of 25OHD onstimulation of bone-resorbing osteoclasts via upregulatingthe RANKL in osteoprogenator cells, osteoblast precursors,and mature osteoblasts, at the same time downregulating theosteoclastogenesis inhibitory factor/osteoprotegrin produc-tion, thus leading to more bone resorption [10].

The extent of VDD found in this study is similar to thatreported by Mansoor et al. in healthy population from atertiary care hospital in Pakistan [5]. Vitamin D deficiencydecreases calcium absorption from the gut, and to maintainserum calcium levels, parathyroid gland was stimulated toraise parathyroid hormone (PTH) level. High PTH increasesthe catabolism of 25OHD, thus further decreasing its bloodlevels. In our study subjects, secondary hyperparathyroid-ism was seen in 25.9 %. However, elevated bone turnoverequally affected subjects with and without sHPTH. The

Table 2 Determinants of NTx;multiple linear regressions

p value<0.05 statisticallysignificantaUnstandardized coefficientbConfidence intervalcLog-transformed plasma iPTHdExposure to sun/week <30 and30–60 mineExposure to sun/week <30 and>60 min

Variables Univariate Final model (p value<0.001)

B* (95 % CI) p value Ba (95 % CI) p value

Serum 25OHD 0.013 (0.003 to 0.023) 0.009 0.013 (0.003 to 0.023) 0.009

Exposure sun/weekd −0.126 (−0.247 to −0.004) 0.043 −0.278 (−0.436 to −0.119) 0.001

Exposure sun/weeke −0.02 (−0.091 to 0.051) 0.586 −0.151 (−0.244 to −0.059) 0.001

Veil status −0.163 (−0.307 to −0.019) 0.027 −0.195 (0.341 to 0.050) 0.009

iPTHc 0.05 (−0.078 to 0.179) 0.439 0.096 (−0.031 to 0.223) 0.139

Age 0.001 (−0.008 to 0.009) 0.908 −0.003 (−0.013 to 0.006) 0.476

BMI −0.008 (−0.021 to 0.005) 0.228 −0.005 (−0.019 to 0.009) 0.462

Ethnicity 0.014 (−0.03 to 0.059) 0.528

Exercise 0.067 (−0.077 to −0.212) 0.360


difference in mean serum NTx levels was not different inthese groups, (18.5 and 19.6 nMBCE/L; p value00.5). Itwas previously suggested that sHPTH might play an impor-tant role in the development of increased bone remodelingand bone loss in females with low 25OHD. However, liter-ature shows that a “blunted” PTH response to VDD iscommon, occurring in up to 75 % of subjects [5, 11]. Weobserve this response in 74 % of females for which the causeis not readily apparent. High calcium intake even with low25OHD levels may have served to keep PTH levels withinnormal limits. It is important to evaluate calcium consump-tion in this group of subjects to draw the conclusion. Theother hypothesis that can be applied here is that 25OHDdeficiency in healthy females is associated with an increasein PTH still within the normal range and able to correct themetabolic imbalance mainly through its action on kidney,while the initial mineralization defect is apparently associ-ated with a somewhat impaired osteoclastic activity. Thisassociation has been reported very recently using differentbone turnover markers [9, 12]. The last reason we couldpropose is magnesium deficiency in these subjects as sug-gested by Sahota et al. [11].

We have found an inverse correlation between 25OHD andiPTH (r0−0.199; p value00.009) with highmean iPTH levelsin VDD as compared to vitamin D sufficient. Similar correla-tion is recently reported on Indian population (r0−0.18; pvalue<0.001) [13] and in previous studies on ambulatoryand healthy premenopausal females [5, 9, 12, 14–17].

Increasing age is a well-identified fixed risk factor forbone health [9, 14]. We did not find any significant associ-ation of ageing with serum NTx (Table 2). On the otherhand, ageing is one of the most significant explanatoryvariables for iPTH levels (r00.168; p value00.027) and thiswas similar to Indian adult females [18]. Despite the factthat all the females recruited in the study are apparentlyhealthy, almost all of them were found to be VDD.However, subjects above 30 years of age had high mean25OHD blood levels as compared to those below 30 years ofage (16.5 vs 14.5 ng/ml). Age is one of the most significantexplanatory variables for PTH levels (r00.168; p value00.027), well correlated with body mass index in our study(r00.39; p value<0.001), which is in accordance to the fifthTromsø study [19].

BMI is an important determinant of bone health infemales [9, 14, 15]. Evidence supports that individuals withsevere deviations from mean BMI have disturbances in bonebalance [20, 21]. In our study, serum NTx and 25OHDblood levels did not differ significantly with BMI, althoughobese females had high iPTH (r00.169, p value00.026).Although several cross-sectional studies have reported astrong inverse association between obesity and 25OHD aswell as a direct association between obesity and PTH [20,22, 23], the link between BMI and iPTH is only of a

statistical importance which does not necessarily imply acause and effect relationship. We found the same relationbetween BMI and iPTH (r00.169, p value00.026) as foundpreviously in study by Kamycheva et al., a large epidemio-logical study [19]. Overweight can be due to increase PTHwhich stimulates renal hydroxylation of 25OHD to1,25OHD which in turn elevates calcium influx into adipo-cytes enhancing lipid storage in fat tissue [24, 25]. Secondly,the elevated PTH in obesity is due to deranged renal han-dling of calcium, leading to negative calcium balance andthus elevated PTH [26]. A decrease in PTH with weight lossin obese subjects both on low calorie diet [26] and aftergastric banding [27] is seen.

Ethnicity has been shown to affect bone health [28].Minor differences in bone turnover due to ethnicity havebeen reported between Pakistanis and Norwegians, despite astrikingly different prevalence of sHPTH due to VDD [29].Glover et al. [30] and Blumsohn et al. [31] did not findvariation in turnover in different ethnicity among differentnations. In our study, mean NTx did not differ among ethnicgroups despite distinct variations for mean 25OHD andiPTH levels; with Pathan females having strikingly low25OHD and high iPTH levels. This variation in the preva-lence of hypovitaminosis D between different ethnic groupsmay be explained partly by differences in skin color andcultural behaviors. That cultural behavior may explain vita-min D variations linked to nutritional and religious differ-ences between people of different origin but living in thesame city [32].

High bone turnover was pronounced in females expose tosun for <30 min per week but the duration of sun exposuredid not have a significant association with 25OHD andiPTH levels, though Karachi is located in the south ofPakistan, on the coast of the Arabian Sea on latitude 24°51′ N where sunshine is 280 h/month during winter and304 h/month during summer. Previous studies suggestedlack of sunlight exposure as a major determinant of highdegree of VDD seen in Pakistani females due to veil ob-serving [3, 4]. Low 25OHD levels were common in bothveil observer and non-observer females as witnessed recent-ly in other Muslim females [15, 33]. However, there is avariation in the definition of veil practice among variousstudies in the literature. The majority of Pakistani femalesmaintained a conservative clothing style while being out-door covering the entire body, with variations only in thecoverage of the face and hands. Thus, small contribution ofthe exposed body area to the extent of cutaneous synthesisof vitamin D explains the insignificant difference amongveil observer or non-observer premenopausal females.Recently, air pollution hindering the availability of UVBfrom sunlight has been proposed as a hypothesis for theprevalence of high VDD in industrial cities. Air pollution isone of the foremost factors in determining the percentage of


the ground level of UVB. The level of air pollution isinversely related to the extent of solar UVB that reachesEarth's surface. Therefore, less UVB will be available inmore polluted areas resulting in lower vitamin D cutaneoussynthesis. Evaluation of air pollution is beyond the scope ofthis research. The questionnaires used in this study onsunlight exposure were crude estimation which may bedeceptive. The use of a more direct method such as ultravi-olet dosimetry for assessing sunlight levels may be useful toexplore this as a determinant of VDD in our population [34,35].

There is a need to carry out a large epidemiological studyin the community for assessing the disease burden. A majorlimitation of this study is a relatively sample size, theabsence of a population-based sampling frame, the absenceof DXA assessment of bone density, and the uncertainthresholds utilized for estimations of NTx. The risk assess-ment model for determining osteoporosis for our populationmay be different from the west. A daunting task would be toassess the risk factors for poor bone health of the communityin Pakistan and to translate it into a model for assessingosteoporosis, with meager resources.

Acknowledgments This research was funded by the URC (URCproject ID # 072016P&M) and resident seed money program forresearch development (2007) from the Department of Pathology &Microbiology, Aga Khan University.

Conflict of interest None.

Other disclosures This paper is a part of dissertation approved andaccepted on 26 June 2010 by Research Training and Monitoring Cell,College of Physicians and Surgeons Pakistan for Fellowship of theCollege of Physicians and Surgeons in the field of Chemical Pathologyby Dr. Farhan Javed Dar. The dissertation/project was supervised byDr. Aysha Habib Khan. The abstract was accepted for oral presentationat 4th National Conference, Pakistan Society of Chemical Pathologist,held at Allama Iqbal College, Lahore on 25–26 February 2011 and as aposter in American Society of Bone and Mineral Research annualmeeting 2010, Toronto, Canada on 15–19 October 2010 (SA0349).Preliminary data of this project on 78 subjects were presented at 32ndAnnual Conference, Pakistan Association of Pathologists held at AyubMedical College, Abbottabad, Pakistan on 24–26 October 2008, andalso in Health Research Assembly 2008, Aga Khan University Karachion 19 December 2008.

References

1. Perez-Lopez FR (2007) Vitamin D and its implications for mus-culoskeletal health in women: an update. Maturitas 58(2):117–137

2. Landry CS, Ruppe MD, Grubbs EG (2011) Vitamin D receptorsand parathyroid glands. Endocr Pract 17(Suppl 1):63–68

3. Gannage-Yared MH, Chemali R, Yaacoub N, Halaby G (2000)Hypovitaminosis D in a sunny country: relation to lifestyle andbone markers. J Bone Miner Res 15(9):1856–1862

4. Mahmood K, Akhtar ST, Talib A, Haider I (2009) Vitamin-Dstatus in a population of healthy adults in Pakistan. Pak J MedSci 25(4):545–550

5. Mansoor S, Habib A, Ghani F, Fatmi Z, Badruddin S, Siddiqui I etal (2010) Prevalence and significance of vitamin D deficiency andinsufficiency among apparently healthy adults. Clin Biochem 43(18):1431–1435

6. Wu XY, Wu XP, Xie H, Zhang H, Peng YQ, Yuan LQ et al (2010)Age-related changes in biochemical markers of bone turnover andgonadotropin levels and their relationship among Chinese adultwomen. Osteoporos Int 21(2):275–285

7. Miyabara Y, Onoe Y, Harada A, Kuroda T, Sasaki S, Ohta H(2007) Effect of physical activity and nutrition on bone mineraldensity in young Japanese women. J Bone Miner Metab 25(6):414–418

8. Baca EA, Ulibarri VA, Scariano JK, Ujah I, Bassi A, Rabasa AI etal (1999) Increased serum levels of N-telopeptides (NTx) of bonecollagen in postmenopausal Nigerian women. Calcif Tissue Int 65(2):125–128

9. Adami S, Bertoldo F, Braga V, Fracassi E, Gatti D, Gandolini G etal (2009) 25-Hydroxy vitamin D levels in healthy premenopausalwomen: association with bone turnover markers and bone mineraldensity. Bone 45(3):423–426

10. Blair HC, Robinson LJ, Huang CL, Sun L, Friedman PA,Schlesinger PH et al (2011) Calcium and bone disease. Bio-factors 37(3):159–167

11. Sahota O, Mundey MK, San P, Godber IM, Hosking DJ (2006)Vitamin D insufficiency and the blunted PTH response in estab-lished osteoporosis: the role of magnesium deficiency. OsteoporosInt 17(7):1013–1021

12. Glover SJ, Garnero P, Naylor K, Rogers A, Eastell R (2008)Establishing a reference range for bone turnover markers in young,healthy women. Bone 42(4):623–630

13. Shivane VK, Sarathi V, Bandgar T, Menon P, Shah NS (2011)High prevalence of hypovitaminosis D in young healthyadults from the western part of India. Postgrad Med J87:514–518

14. Allali F, El Aichaoui S, Khazani H, Benyahia B, Saoud B, ElKabbaj S et al (2009) High prevalence of hypovitaminosis D inMorocco: relationship to lifestyle, physical performance, bonemarkers, and bone mineral density. Semin Arthritis Rheum 38(6):444–451

15. Ardawi MS, Qari MH, Rouzi AA, Maimani AA, Raddadi RM(2011) Vitamin D status in relation to obesity, bone mineral den-sity, bone turnover markers and vitamin D receptor genotypes inhealthy Saudi pre- and postmenopausal women. Osteoporos Int 22(2):463–475

16. Islam MZ, Shamim AA, Kemi V, Nevanlinna A, AkhtaruzzamanM, Laaksonen M et al (2008) Vitamin D deficiency and low bonestatus in adult female garment factory workers in Bangladesh. Br JNutr 99(6):1322–1329

17. Madar AA, Stene LC, Meyer HE (2009) Vitamin D status amongimmigrant mothers from Pakistan, Turkey and Somalia and theirinfants attending child health clinics in Norway. Br J Nutr 101(7):1052–1058

18. Desai MP, Bhanuprakash KV, Khatkhatay MI, Donde UM (2007)Age-related changes in bone turnover markers and ovarian hor-mones in premenopausal and postmenopausal Indian women. JClin Lab Anal 21(2):55–60

19. Kamycheva E, Sundsfjord J, Jorde R (2004) Serum parathyroidhormone level is associated with body mass index. The 5th Tromsostudy. Eur J Endocrinol 151(2):167–172

20. Rejnmark L, Vestergaard P, Brot C, Mosekilde L (2008) Parathy-roid response to vitamin D insufficiency: relations to bone, bodycomposition and to lifestyle characteristics. Clin Endocrinol (Oxf)69(1):29–35


21. Lagunova Z, Porojnicu AC, Vieth R, Lindberg FA, Hexeberg S,Moan J (2011) Serum 25-hydroxyvitamin D is a predictor of serum1,25-dihydroxyvitamin D in overweight and obese patients. J Nutr141(1):112–117

22. Arunabh S, Pollack S, Yeh J, Aloia JF (2003) Body fat content and25-hydroxyvitamin D levels in healthy women. J Clin EndocrinolMetab 88(1):157–161

23. Snijder MB, van Dam RM, Visser M, Deeg DJ, Dekker JM, BouterLM et al (2005) Adiposity in relation to vitamin D status andparathyroid hormone levels: a population-based study in oldermen and women. J Clin Endocrinol Metab 90(7):4119–4123

24. Shi H, Dirienzo D, Zemel MB (2001) Effects of dietary calcium onadipocyte lipid metabolism and body weight regulation in energy-restricted aP2-agouti transgenic mice. FASEB J 15(2):291–293

25. Zemel MB, Shi H, Greer B, Dirienzo D, Zemel PC (2000) Regu-lation of adiposity by dietary calcium. FASEB J 14(9):1132–1138

26. Andersen T, McNair P, Hyldstrup L, Fogh-Andersen N, NielsenTT, Astrup A et al (1988) Secondary hyperparathyroidism ofmorbid obesity regresses during weight reduction. Metabolism 37(5):425–428

27. Pugnale N, Giusti V, Suter M, Zysset E, Heraief E, Gaillard RC etal (2003) Bone metabolism and risk of secondary hyperparathy-roidism 12 months after gastric banding in obese pre-menopausalwomen. Int J Obes Relat Metab Disord 27(1):110–116

28. Finkelstein JS, Sowers M, Greendale GA, Lee ML, Neer RM,Cauley JA et al (2002) Ethnic variation in bone turnover in pre-and early perimenopausal women: effects of anthropometric andlifestyle factors. J Clin Endocrinol Metab 87(7):3051–3056

29. Holvik K, Meyer HE, Sogaard AJ, Selmer R, Haug E, Falch JA(2006) Biochemical markers of bone turnover and their relation toforearm bone mineral density in persons of Pakistani and Norwe-gian background living in Oslo, Norway: The Oslo Health Study.Eur J Endocrinol 155(5):693–699

30. Glover SJ, Gall M, Schoenborn-Kellenberger O, Wagener M,Garnero P, Boonen S et al (2009) Establishing a referenceinterval for bone turnover markers in 637 healthy, young,premenopausal women from the United Kingdom, France,Belgium, and the United States. J Bone Miner Res 24(3):389–397

31. Blumsohn A, Naylor KE, Timm W, Eagleton AC, Hannon RA,Eastell R (2003) Absence of marked seasonal change in boneturnover: a longitudinal and multicenter cross-sectional study. JBone Miner Res 18(7):1274–1281

32. Holvik K, Meyer HE, Haug E, Brunvand L (2005) Prevalence andpredictors of vitamin D deficiency in five immigrant groups livingin Oslo, Norway: the Oslo Immigrant Health Study. Eur J ClinNutr 59(1):57–63

33. Islam MZ, Akhtaruzzaman M, Lamberg-Allardt C (2006) Hypovita-minosis D is common in both veiled and nonveiled Bangladeshiwomen. Asia Pac J Clin Nutr 15(1):81–87

34. McKinley A, Janda M, Auster J, Kimlin M (2011) In vitro modelof vitamin D synthesis by UV radiation in an Australian urbanenvironment. Photochem Photobiol 87(2):447–451

35. Terenetskaya I (2004) Two methods for direct assessment of theVitamin D synthetic capacity of sunlight and artificial UV sources.J Steroid Biochem Mol Biol 89–90(1–5):623–626


Bone health status of premenopausal healthy adult females in Pakistani females

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