Content uploaded by Constance Hilliard
Author content
All content in this area was uploaded by Constance Hilliard on Jul 07, 2018
Content may be subject to copyright.
ORIGINAL ARTICLE
High osteoporosis risk among East Africans linked
to lactase persistence genotype
Constance B Hilliard
Department of History, University of North Texas, Denton, TX, USA.
This ecological correlation study explores the marked differential in osteoporosis susceptibility between East and West
Africans. African tsetse belt populations are lactase non-persistent (lactose intolerant) and possess none of the genetic
polymorphisms carried by lactase persistent (lactose tolerant) ethnic populations. What appears paradoxical, however,
is the fact that Niger-Kordofanian (NK) West African ethnicities are also at minimal risk of osteoporosis. Although East
Africans share a genetic affinity with NK West Africans, they display susceptibility rates of the bone disorder closer to
those found in Europe. Similar to Europeans, they also carry alleles conferring the lactase persistence genetic traits.
Hip fracture rates of African populations are juxtaposed with a global model to determine whether it is the unique ecology
of the tsetse-infested zone or other variables that may be at work. This project uses MINITAB 17 software for regression
analyses. The research data are found on AJOL (African Journals Online), PUBMED and JSTOR (Scholarly Journal
Archive). Data showing the risk of osteoporosis to be 80 times higher among East Africans with higher levels of lactase
persistence than lactase non-persistence West Africans are compared with global statistics. Hip fracture rates in
40 countries exhibit a high Pearson’s correlation of r¼0.851, with P-value ¼0.000 in relation to dairy consumption. Lower
correlations are seen for hip fracture incidence vis-a
`-vis lactase persistence, per capita income and animal protein
consumption. Ethnic populations who lack lactase persistence single-nucleotide polymorphisms may be at low risk of
developing osteoporosis.
BoneKEy Reports 5, Article number: 803 (2016) | doi:10.1038/bonekey.2016.30
Introduction
Osteoporosis is a degenerative bone disease, which is
characterized by a low skeletal mass, micro-architectural
deterioration of bone tissue and an increased risk of fracture.
It afflicts an estimated 200 million people globally, placing a
heavy burden on financial and health-care resources. Family
and twin studies have identified a strong heritability component
to this disorder. However, one of the most challenging areas of
biogenetics research is the ongoing effort to decode the genetic
signature of this complex bone disorder.
1
Efforts to unmask the osteoporotic disease process by
setting low-risk West Africans side by side with high-risk
Northern Europeans are weighed down by a plethora of
confounding variables. The differences that must be adjusted
for involve not only genetic inheritance but also cultural factors,
lifestyles, diet, habits of physical exertion, socio-economic
status, life expectancy, climate, geography, epidemiological
susceptibilities and qualitative differences in data collection.
This study first examines data on hip fracture incidence among
sub-Saharan African agriculturalists and pastoralists, that is,
Niger-Kordofanians, Nilo-Saharans and Afro-Asiatics, whose
genetic affiliations overlap with their linguistic groupings.
2
Although sharing similar per capita incomes, and life
expectancies, notable differences in osteoporosis rates exist.
2
The appearance of a high correlation between pastoralism or
dairy farming and osteoporosis in Africa is subsequently applied
to a global data set of 40 countries. In addition to looking at the
possible effects of dairy farming on hip fracture rates, it also
applies regression analysis to such independent variables
as lactase persistence single-nucleotide polymorphisms (SNP;
derived from ethnic percentages of lactase persistence),
per capita income and animal protein consumption.
Results
Hip fracture rates for females in the non-dairy, West African
tsetse belt nations of Nigeria and Cameroon average 3.0 hip
fractures per 100 000 for women aged 50 years and older.
3,4
Among these Bantu-speaking (Niger-Kordofanian) agri-
culturalists, the rate of lactase non-persistence is 90 þpercent.
Kenya, on the other hand, is located outside the tsetse zone.
Dairy farming/pastoralism is prevalent, and the rate of
post-menopausal hip fractures averaged 243 per 100 000.
5,6
Correspondence: Professor CB Hilliard, Department of History, University of North Texas, P.O. Box 310650, Denton, TX 76203, USA.
E-mail: connie@unt.edu
Received 8 September 2015; accepted 15 March 2016; published online 29 June 2016
Citation: BoneKEy Reports 5, Article number: 803 (2016) | doi:10.1038/bonekey.2016.30
&2016 International Bone & Mineral Society All rights reserved 2047-6396/16
www.nature.com/bonekey
BoneKEy Reports |JUNE 2016 1
In order to substantiate and expand the scope of these
unusual findings, this study tests potentially meaningful
independent variables, globally, using statistics from Europe,
Asia, North America, Latin America and Africa (Tables 1–3: Data
from 40 countries on hip fracture incidence, dairy consumption,
lactase persistence SNPs, animal protein consumption and per
capita income and references). An analysis using MINITAB 17 to
compute correlations identifies dairy consumption as the
independent variable with the highest Pearson correlation to hip
fractures per 100 000 (r¼0.851 with P-value ¼0.000 (Figure 1:
Fitted Line Plot: Hip Fracture vs Dairy Consumption). The
second highest independent variable, lactase persistence
alleles, is r¼0.735, P-value ¼0.000 (Figure 2 Fitted Line Plot:
hip fracture incidence vs lactase persistence SNPs). The data
on lactase persistence SNPs were derived from Population
percentages that exhibited the LP trait as a function of their
possessing the prescribed SNPs identified with this genotype.
Per capita income and animal protein consumption are
r¼0.634, P-value ¼0.000 (Figure 3: Fitted Line Plot: Hip
Fracture Incidence vs Animal Protein Consumption) and
r¼0.447, P-value ¼0.004 (Figure 4 Fitted Line Plot: Hip
Fracture Incidence vs Per Capita Income). These calculations
were made with a confidence interval of 95%.
Discussion
Genetic researchers using genome-wide association studies,
and newer comprehensive genotyping platforms, have to date
identified 150 candidate genes and SNP found to be associated
with osteoporosis.
7,8
However, that number is expected to rise,
and some researchers now suggest that the final count could
number in the thousands.
9
Currently, the most popular
candidates include genes encoding the vitamin D receptor, the
alpha and beta estrogen receptors, apolipoprotein E, collagen
type I, alpha 1 and methylene tetrahydrofolate reductase,
among others.
10
In short, biogenetic technology has widely
Table 1 Data from 40 countries on hip fracture incidence, dairy consumption per annum, lactase persistence SNPs, animal protein consumption per annum and annual
per capita income
C1-T Country Hip fracture per
100 000
a
Dairy consumption
(kg)
b
Lactase persistence
SNPs
c
Animal protein
(kg)
d
Per capita
income
e
North
America
United States 595 253.8 86.5 126.6 54 370
Canada 310.9 206.83 80 108.1 44 967
Europe United
Kingdom
523.5 241.47 90 83.9 39 826
Ireland 488 247.17 95 106.3 51 284
Sweden 802.8 355.86 95 77.1 46 219
Norway 563 261.52 86 65.7 67 166
Denmark 853 295.62 96 61.7 44 625
Finland 440 361.19 88 67.4 40 661
Iceland 385 223.68 95 84.8 44 029
Netherlands 368.3 320.15 99 89.3 47 960
Belgium 538.7 238.47 85 86.1 43 139
Switzerland 413 315.78 90 72.9 58 149
Germany 522 247.24 82.5 82.1 46 216
France 443 260.48 65 101.1 40538
Spain 353 177.49 85 118.6 33 835
Portugal 408 222.94 75 91.1 27 069
Italy 498.4 256.1 81 90.4 35 131
Malta 502.5 188.64 80 86.9 33 198
Hungary 488 175.59 63 100.7 25 019
Russia 249 172.46 75 51 24 449
Kazakhstan 651.1 260 28.5 56.02 19744
Oceania Australia 295 235.11 90 117.6 46 550
New Zealand 288 110.4 91 104 35 305
Latin
America
Mexico 169 115.18 45 62.2 17 950
Argentina 298 213.1 40 36.5 22 302
Brazil 138 124.61 15 80.5 16 155
Venezuela 150 87.29 20 56.6 17 759
Asia China 97 29.04 5 53.5 13 224
India 159 105.1 36.5 3.3 5808
South Korea 262.8 71.5 10 48.9 35 379
Japan 266 93 2.5 45.4 37 519
Hong Kong 110 13.98 10 133.9 55 097
Thailand 7.05 22.48 2 27.9 15 579
Turkey 357 138.71 29 19.3 19 698
Jordan 198 88.1 25 29.8 11 971
Africa Morocco 85.9 50 27 23.8 7813
Cameroon 3 14.4 5 13.5 3007
Kenya 245 98.64 35 15.4 3009
Nigeria 2 5.4 5 8.6 6054
South Africa 20 57.92 16 39 13 094
References 45,46.
a
See Table 2 for global references on hip fracture incidence per 100,000 per annum.
b
FAO Statistics Division.
47 c
See Table 3 for references. Lactase persistence (LP)
single-nucleotide polymorphisms (SNP) are inferred from calculations of percentage of LP in national or ethnic populations.
d
FAO.
48 e
International Monetary Fund.
49
High osteoporosis risk among East Africans
CB Hilliard
2JUNE 2016 |www.nature.com/bonekey
increased our knowledge base of potential candidate genes for
osteoporosis. However, the statistical power of such studies
remains limited in their ability to assess gene–environment
interaction.
11
By shifting focus from the West, where this
degenerative bone disorder is most prevalent, to Africa, where it
is virtually unknown in some regions, but common in others, this
study presents new insights into the disorder’s etiology and its
signature marker genes.
A unique phenomenon found in sub-Saharan Africa provides
a natural laboratory for examining osteoporosis. An environ-
mental line of demarcation runs through the continent,
appearing to divide low osteoporotic risk West Africa from
higher risk East Africa. It tracks the boundaries of the vast
swathe of West and Central Africa infested by the tsetse fly
glossina, which transmits parasites of the Genus Trypanosoma
(Figure 5 Map of Sub-Saharan African Tsetse Zone & Cattle
Rearing Areas).
12
This tsetse-infected area covers nearly one-
third of the African continent or roughly 10 million km
2
, including
some of the most fertile and best watered regions of
West Africa.
13
Pastoralism is not possible in this zone. Although
these parasites cause relatively mild infections in wild animals,
in domestic livestock they cause a severe, often fatal disease,
referred to as nagana.
12
The exception is the trypanotolerant
cattle breeds maintained by Fulbe pastoralists on the margins of
the zone.
14
Humans, however, show some level of resistance to
all African trypanosome species with the exception of
Trypanosoma brucei gambiense and T. b. rhodesiense.
15
The lack of osteoporosis risk found among the Niger-
Kordofanian (Bantu-speaking) populations of West Africa may
also help in reconstructing the etiology of this degenerative
bone disorder. That is, the intersection of historical and genetic
data may be able to shed light on the evolutionary epoch in
which it began appearing among non-Niger-Kordofanian
humans. According to the consensus ‘Recent African Origin’
model, anatomically modern humans evolved in Africa around
200 Kya (thousand years ago). The Niger-Kordofanian Africans
(Y-DNA Haplogroup E1b1a, also known as the E-V38 phylo-
genetic tree) have lived continuously on the continent from
earliest times.
16
If osteoporosis was not part of this ethnicity’s
bone morphology, when did it creep into the human genome?
Several research studies have proposed that human sus-
ceptibility to osteoporosis and osteoporosis-related fractures is
Table 2 References used to compute hip fracture incidences per 100 000
Country Citation
Argentina
50
Australia
51
Belgium
52
Brazil
53
Cameroon
4
Canada
54
China
55
Denmark
56
Finland
57
France
58
Germany
59
Hong Kong
60
Hungary
61
Iceland
62
India
60
Ireland
63
Italy
63
Japan
64
Jordan
65
Kazakhstan
66
Kenya
6
Malta
63
Mexico
55
Morocco
67
Netherlands
63
New Zealand
68
Nigeria
3
Norway
69
Portugal
70
Russia
71
South Africa
72
South Korea
73
Spain
74
Sweden
75
Switzerland
64
Thailand
76
Turkey
77
United Kingdom
78
United States
79
Venezuela
80
Table 3 References used to compute lactase persistence (LP) single-nucleotide
polymorphisms (as a function of LP ethnic percentages)
a
(Multiple sources were
averaged)
Country Citation
Argentina
81
Australia
82
Belgium
83
Brazil
84
Cameroon
85
Canada
86
China
87
22
Denmark
88
Finland
89
France
90
Germany
90
Hong Kong Duplicated from China data
Hungary
91
Iceland Duplicated from Sweden data
India
92
Ireland
85
Italy
93
Japan
94
Jordan
95
Kazakhstan
87
Kenya
96
Malta Duplicated from Spain data
Mexico
90
Morocco
97
Netherlands
83
New Zealand
98
Nigeria
82
Norway
99
Portugal
100
Russia
95
South Africa
101
102
South Korea Duplicated from China data
Spain
103
Sweden
104
Switzerland
82
Thailand
82
Turkey
85
United Kingdom
90
United States
105
Venezuela
81
a
These data on lactase persistence (LP) single-nucleotide polymorphisms (SNPs)
were derived from population percentages that exhibited the LP trait as a function
of their possessing the prescribed SNPs identified with this genotype.
High osteoporosis risk among East Africans
CB Hilliard
BoneKEy Reports |JUNE 2016 3
the result of evolutionary adaptation, in which clues might be
found in weighing the selective advantages and disadvantages
of changed environments or human ecology.
17,18
This study’s transdisciplinary approach takes up that
challenge by identifying the African tsetse/non-tsetse
geographic divide, which appears to have played a role in
differentiating low- and high-risk osteoporotic populations.
Although the post-menopausal hip fracture rate and lactase
persistence trait among East African pastoralists are closer to
those of Europeans, their phylogenetic classifications—
Khoisan, Niger-Kordofanian, Nilo-Saharan and Afro-Asiatic—
are African.
19
The osteoporotic susceptibility of East Africans
also appears to correlate with recently identified alleles,
encoded by the mini-chromosome maintenance protein 6
(MCM6), which influences the nearby lactase (LCT) gene.
This genetic variant produces the lactase-phlorizin hydrolase
enzyme in the gut wall, which regulates the absorption of
lactose, the main sugar component in milk.
Western researchers had once assumed that lactase
persistence represented a global genotype because of the
ubiquitous nature of dairy culture among the European
populations with which they were most familiar. However, the
contrary has turned out to be the case, with 65% of the world’s
population exhibiting the lactase non-persistence trait.
20
As for
what populations have these alleles and why, the answers have
come through a series of studies examining genetic variation
between dairy and non-dairy societies. Recent studies have
shown that farming cultures have evolved the genetic variants
required to allow adults to consume milk.
21
In the case of
Northern Europeans, the T allele of a SNP 13.9 kb upstream of
the lactase gene 13910-T/T allele (also known as 13910-T/T or
rs4988235-T) confers the lactase persistence trait and is found
in 90–95% of this population group. Individuals carrying the
13910 C/T and 13910 C/C (rather than 13910-T/T) SNPs are
likely to be lactase non-persistent. Another set of genetic
variants found among certain Europeans, the Kazakhstanis and
populations inhabiting Northern India is the 22018A (also known
as rs182549) SNP, which confers the lactase persistence
trait and 22018-G, associated with the lactase non-persistent
genotype.
22
Further research by the team of Sarah Tishkoff et al has
shown that the genetic variants found among Europeans differ
from those found in African dairying populations. East African
Figure 3 A Fitted Line Plot showing the correlation between Hip Fracture rates per
100 000 and Animal Protein Consumption, using data from 40 countries in Africa,
Europe, Latin America, North America, Asia and Oceania.
Figure 1 A Fitted Line Plot showing the correlation between Hip Fracture rates per
100 000 and Dairy Consumption, using data from 40 countries in Africa, Europe, Latin
America, North America, Asia and Oceania.
Figure 2 A Fitted Line Plot showing the correlation between Hip Fracture rates per
100 000 and the percentage of populations in 40 countries in Africa, Europe, Latin
America, North America, Asia and Oceania, who display the lactase persistence (LP)
genotype, which signals the presence of LP single-nucleotide polymorphisms.
Figure 4 A Fitted Line Plot showing the correlation between Hip Fracture rates per
100 000 and per capita income, using data from 40 countries in Africa, Europe, Latin
America, North America, Asia and Oceania.
High osteoporosis risk among East Africans
CB Hilliard
4JUNE 2016 |www.nature.com/bonekey
ethnicities possess any of three of these LCT-associated SNPs
(14010-G/C, 13915-T/G and 13907-C/G) in their genomes. They
endow this group with the lactase persistence trait.
23
The
dominant lactase persistence polymorphism identified in Africa
(c-14010) was found among Afro-Asiatic, Nilo-Saharan and
Niger-Kordofanian populations at rates of 42.1%, 38.3 and 25%
frequency. As expected, the East African branch of the
Niger-Kordofanian group of farmers and agro-pastoralists had
the smallest percentage of this dairy-derived SNP relative to the
pastoralist populations. However, the West African Yoruba of
Nigeria, which also belongs to the Niger-Kordofanian linguistic
group, showed ‘0’ percent frequency of the lactase persistence
polymorphism C-14010.
24
Bypassed by MCM6 mutation
Inhabiting the tsetse zone, with its special entomological
challenges, the Niger-Kordofanians were passed over by one of
the most significant developments in recent evolutionary
genetics—the dairy revolution.
21
This transition from cereal-
grain agriculture to dairy pastoralism/farming swept through
Europe, as well as parts of the Middle East and East Africa
11 000 years ago. The genomic consequences were significant
and swift. Within two millennium, several mutations had
emerged and spread rapidly, allowing adults in dairy regions to
hydrolyze the lactose in milk without first having to ferment it.
The introduction of milk products to the human food supply
increased calcium intake in dairy societies by 190%. Although
the norm in Western countries rose to 700–800mg, dietary
calcium intake for populations in the tsetse zone remained in the
200–400 mg. a day range.
25
In comparison, the pastoralist Masai
of East Africa have developed average daily intake of dairy
calcium as high as 6000–7000 mg, based on a bovine milk diet.
Genetic studies also showed that, among Europeans, even
the five to fifteen percent of such populations who exhibited
the lactase non-persistence genotype nonetheless carried a
variant of the lactase persistence allele. On the other hand,
no lactase persistence variants were found in the West African
Niger-Kordofanian population groups.
Osteoporosis in east and west Africa
Many West African-trained physicians in the tsetse belt have
never seen, let alone treated a case of post-menopausal
osteoporosis. However, their East African counterparts declare
themselves to be facing an epidemic of such traumatic hip
fractures, particularly among the agro-pastoralist population of
Kenya.
26
In fact, a 2008 study in the British Journal of Sports
Figure 5 A map highlighting the cattle/dairy farming regions and the Tsetse Fly Belt in Sub-Saharan Africa.
High osteoporosis risk among East Africans
CB Hilliard
BoneKEy Reports |JUNE 2016 5
Medicine underscored the fact that osteoporosis has a pre-
sence in East Africa. It described the case of an elite Kenyan
marathon runner, who presented at a London hospital with an
osteoporotic fracture of the tibia, sustained during an inter-
national cross-country race.
27
Although this man’s case was
singular, it did support the findings in two studies conducted by
Kenyan doctors. One was a report prepared by Dr G. Omondi
Oyoo, a Rheumatologist and Senior lecturer at the University of
Nairobi (Kenya) entitled: ‘Stemming the tide of an osteoporosis
epidemic.’
26
The second was a 2004 study, ‘Is There Osteo-
porosis in Kenya?’ in which Odawa et al.
6
reported a diagnosis
of osteoporosis among 24.3% of postmenopausal women and
osteopenia in 32%. In 2010, Dr LN Gakuu
28
of the Department of
Orthopaedic Surgery, in the University of Nairobi College of
Health Sciences, announced that osteoporosis had reached a
crisis point and that all patients over 75 years of age with fragility
fractures should be empirically treated for the bone disorder.
29
Among pre-menopausal women, the rates were 0.9% and
20.5%, respectively.
6
The Kenyan rate of osteoporosis for
women 50 years of age and over averaged 243 per 100 000.
6
The West African experience with osteoporosis appears to be
uniquely different. A 2014 Nature study reviewing hip fracture
incidence worldwide included a chart of age-standardized
osteoporosis rates. The Nigerian values were 2 hip fractures per
100 000 females, whereas that of Norway was 532.
3,30
A 2-year
project conducted by Zebaze et al.
31
in the West African nation
of Cameroon, which was published in 2003, reported a
low-energy trauma fracture rate for females over 35 at 4.1 per
100 000. The unusually low susceptibility rate for the West
African nations did not raise eyebrows in the medical com-
munity because researchers had theorized as early as 1966 that
Africans did not suffer from postmenopausal osteoporosis
because of a short life expectancy, a more active lifestyle than
industrialized westerners and the lack of medical facilities to
treat and record osteoporotic disease.
28,32
However, none
of these assumptions proved valid when osteoporosis rates
were compared within regions of Africa, sharing similar life
expectancies and socio-economic conditions.
Animal protein and osteoporosis
The identification of candidate genes involved in the immediate
pathogenesis of osteoporosis lies beyond the scope of
this study, which, instead, examines broad ecological and
evolutionary patterns of osteoporotic susceptibility. However,
in recent years, a growing number of medical researchers
have endorsed what is commonly referred to as the ‘acid-ash’
theory. It stipulates that low circulating 25-hydroxyvitamin D,
caused by excess acidity produced during the metabolism
of animal protein, raises the risk of osteoporosis.
33
However,
the correlation analyses presented in this paper suggest
that animal protein may not be as pivotal a factor in the
disease’s etiology as dairy calcium (Figures 1 and 3). It is
generally true that the consumption of animal protein is greatest
in the West, where susceptibility to osteoporosis is highest.
34
Dairy farming and beef consumption are naturally correlated,
as the availability of cows for dairy farming enhances the
availability of beef in the food supply. The one exception does
represent 17% of the global human population—India.
Although that country’s inhabitants consume 105.10 kilograms
of dairy per capita each year, the consumption of animal
protein for this predominantly vegetarian nation is only
3.3 kilograms. Osteoporosis is widely prevalent in India and is a
common cause of morbidity and mortality in both men and
women.
31,35
Data reliability
In comparing hip fracture rates among the African ethnicities,
this study has eliminated some of the confounding factors that
might otherwise arise in comparing osteoporotic risk among
culturally diverse European and African populations. It then
compares these findings with a regression analysis of hip
fracture rates and several relevant independent variables
on a global basis (Figure 6). However, attesting to the reliability
of what appear to be such marked differences in post-
menopausal hip fracture rates between East Africa (Kenya-243)
and West Africa (Cameroon-3) when the data are so scanty
requires a different approach.
For nearly three decades, medical researchers had grappled
with the ‘paradox’ of African-Americans being deemed
calcium deficient by national nutritional standards, while
suffering the lowest rate of osteoporosis and highest bone
mineral density (BMD) levels of any American ethnic group.
36,37
In terms of genetic ancestry, American blacks are an admixed
ethnic population of B80% West African/Niger-Kordofanian
and B20% European ancestral quanta. Their low dairy
consumption rate is attributable to the fact that 70% of this
population is also lactase non-persistent.
38
However, a series of clinical studies begun in the 1990s
showed that Black children and adults excreted less urinary
calcium than whites on essentially the same diets and
consequently retained more calcium in their skeletons.
39
Greater calcium retention generated faster rates of bone
growth during adolescence. Also, parathyroid hormone
concentrations did not result in increased bone loss as seems
to be the cause in European ethnicities that have been
studied, because of skeletal resistance to that hormone.
39
In short, the more efficient process of calcium homeostasis
found in the physiology of this low to non-dairy consuming
ethnic population more than made up for the reduced dietary
calcium intake.
39
African-Americans’ verifiably low rate of
osteoporosis did in fact support the sketchy data pointing to
their Niger-Kordofanian genetic ancestors’ low susceptibility
to the disease.
*Pearson Correlations anal
y
zes usin
g
MINITAB 17, from data
p
resented in Table 1
Figure 6 A graph depicting the degree of correlation between Hip Fracture Rates
per 100 000 and 5 independent variables: dairy consumption, lactase persistence,
animal protein consumption, per capita income and habitation in tsetse or non-tsetse
zones.
High osteoporosis risk among East Africans
CB Hilliard
6JUNE 2016 |www.nature.com/bonekey
Hip fracture vs BMD
Hip or femoral fracture rates are used in this study because this
fragility fracture pattern is commonly applied in diagnosing
osteoporosis. It is often due to a fall or minor trauma in someone
with weakened osteoporotic bone. Also, as a point of
clarification, this study relies on hip fracture rather than BMD
data, whose lumbar and spinal measures are used in the US and
Europe to diagnose osteoporosis in women with low bone
density. Although low rates of BMD have correlated with high
susceptibility to osteoporosis among European populations, a
series of studies have shown this not to be the case among all
ethnicities. Blacks in South Africa as well as the West African
nation of Gambia have exhibited BMD measurements lower
than those of age-matched Whites, but these groups retained
low osteoporosis rates.
40
Also, BMD data were not available in
the areas covered by this study. Only one dual-energy X-ray
absorptiometry scanner, used to diagnose BMD, exists in the
entire East Africa region of 131.1 million inhabitants.
41
Although
the development of the Fracture Risk Assessment Tool
algorithm by the World Health Organization has improved
osteoporosis detection in other parts of the world, Kenya is one
of the few African nations that has adopted the less technology-
dependent Fracture Risk Assessment Tool.
42
Materials and Methods
This study uses ecological correlation modeling to assess associations
between post-menopausal female hip fracture rates and factors
identified by comparing sub-Saharan populations and a global
sampling with differing osteoporotic risks. The pinpointed independent
variables include per capita dairy consumption, lactase persistence
alleles, animal protein consumption, per capita GDP and location in
or outside the African tsetse belt. Pearson correlations and Fitted
Line/Scatter Plots produced using MINITAB 17 software (Figure 6). In
the absence of fracture registries in Africa, this research uses data and
observations found in AJOL (African Journals Online—an index of peer-
reviewed African scholarly journals based in South Africa).
43
For the
global distribution of age-adjusted hip fracture risk, per capita dairy,
animal protein consumption and lactase persistence alleles, it uses an
interdisciplinary review of epidemiological and medical literature found
in a search of PUBMED and JSTOR (Scholarly Journal Archive), which is
a digitized library of academic articles in history, geography and a wide
variety of other disciplines (Tables 1 and 2). The search period dated
from 1 January 1970 to 30 April 2015. The terms, some of which had
been searched singly then merged through the use of AND, were taken
from peer-reviewed articles and included the following keywords:
osteoporosis, hip fracture, fragility fracture and Africa, ethnic,
blacks in US, tsetse fly, tsetse belt, trypanosomiasis, LCT, MCM6
polymorphisms, C/T 13 910, C-14010, G-13907, G-13915 genotype,
lactase persistence/lactose tolerance, lactase non-persistence/lactose
intolerance, hypolactasia, l tsetse fly dairy, milk production, milk
consumption, calcium homeostasis, Africa, African-Americans, India,
global and NHANES.
Conclusion
Most genetic research involved in identifying osteoporotic-
candidate genes has not targeted the MCM6 gene or its
LCT-associated SNPs as critical factors. Although this
regression study does show an association between dairy
pastoralism/farming, osteoporotic risk and the possession of
lactase persistence alleles, the correlations do not in and of
themselves establish a causal relationship between the two
variables. However, when the differential osteoporosis rates of
East and West Africans are juxtaposed with studies showing
global correlations and a more efficient calcium homeostasis
among low dairy consuming African-American descendants of
Niger-Kordofanians, the evolutionary link between hip fracture
rates and dairy consumption becomes compelling.
However, a caveat must also be acknowledged here. This
project has called attention to the importance of differentiating
the lactase non-persistence genotype found among non-dairy
consuming ethnic groups from that found in Northern European
individuals, who carry a variant of the lactase persistence
polymorphism. Some level of dairy consumption may be
needed to support bone health in Europeans, East Africans,
Middle Easterners and others who carry this LCT-associated
allele.
44
However, the same prescription might prove less than
beneficial in lactase non-persistence ethnic populations, whose
bone health or that of their descendants could be compromised
by calcium overload. Thus, an additional issue in need of further
study is the long-term consequences of feeding dairy products
to those lactase non-persistence populations who exhibit high
levels of bone health and low osteoporotic risk on account of
biological differences in calcium homeostasis.
Lactase persistence and lactase non-persistence traits may
be used to estimate osteoporosis risk in aggregated ethnic
populations. However, these phenotypes do not determine the
disease risk of self-identified members of ethnic groups, who
have not been genetically tested for the presence of the
requisite gene variants.
This research also identifies a simple, phenotypic criterion for
determining osteoporotic susceptibility in ethnic populations—
lactase non-persistence. Its predictive value will aid in
determining which developing nations should allocate
future public health resources to osteoporosis. The current
assumption that this bone disorder is a function of attaining
higher standards of living and increased animal protein
consumption is not borne out by the data. These findings
also suggest that ethnic minorities in the West who are lactase
lactase non-persistent may benefit from lower dietary calcium
levels than lactase persistence majority populations.
Conflict of Interest
The author declares no conflict of interest.
Acknowledgements
I offer my gratitude to those colleagues who have given
generous encouragement to this research project. They are
Dr Joseph Oppong, Professor of Medical Geography at the
University of North Texas, Marjorie Elizabeth Starkman, MD,
Assistant Professor of Medicine emerita, Division of
Endocrinology and Metabolism, Albany Medical College and
Dr Oluwadiya Kehinde, Consultant Orthopaedic Surgeon and
Traumatologist, Faculty of Clinical Sciences, College of
Medicine, Ekiti State University, and Ekiti State University
Teaching Hospital, Ado-Ekiti, Ekiti State, Nigeria.
References
1. Alonso N, Ralston SH. Unveiling the mysteries of the genetics of osteoporosis. J Endocrinol
Invest 2014; 37: 925–934.
2. Campbell MC, Tishkoff SA. African genetic diversity: implications for human demographic
history, modern human origins, and complex disease mapping. Rev Genomics Hum Genet
2008; 9: 403–433.
High osteoporosis risk among East Africans
CB Hilliard
BoneKEy Reports |JUNE 2016 7
3. Adebajo AO, Cooper C, Evans JG. Fractures of the hip and distal forearm in West Africa and
the United Kingdom. Age and Ageing 1991; 20: 435–438.
4. Zebaze RMD, Seeman E. Epidemiology of hip and wrist fractures in Cameroon, Africa.
Osteoporos Int 2003; 14: 301–305.
5. Oyoo GO, Kariuki JG. Osteoporosis-from hormal replacement therap7 to bisphosphonates
and beyond: a review. East African Med J 2008; 84: 535.
6. Odawa F, Ojwang S, Muia N. The prevalence of post menopausal osteoporosis in black
Kenyan women. J Obstet Gynaecol 2004; 17(Supp 1): 45–46.
7. Richards JB, Zheng H-F, Spector TD. Genetics of osteoporosis from genome-wide
association studies: advances and challenges. Nat Rev Genet 2012; 13: 576–588.
8. Zmuda YT, Sheu SP, Moffett J. The search for human osteoporosis genes J.M. Musculoskelet
Neuronal Interact 2006; 6: 3–15.
9. Clark GR, Duncan EL. The genetics of osteoporosis. Br Med Bull 2015; 113: 73–81.
10. Richards JB. Collaborative meta-analysis: associations of 150 candidate genes with
osteoporosis and osteoporotic fracture. Ann Intern Med 2009; 151: 528.
11. Zmuda JM, Cauley JA, Ferrell RE. Recent progress in understanding the genetic susceptibility
to osteoporosis. Genet Epidemiol 1999; 16: 356–367.
12. Steverding D. The history of African trypanosomiasis. Parasit Vectors 2008; 1: 7http://
www.parasitesandvectors.com/content/1/1/3. (Accessed on December 2015).
13. MacLennan KJR, Putt SNH, Na’isa SNH, Toure SM. ‘Tsetse Transmitted Trypanosomiasis.
Joint IFS/ILCA workshop on small ruminant research in the tropics. http://www.fao.org/
wairdocs/ilri/x5539e/x5539e08.htm. (Accessed on January 2016).
14. Mattioli R, Feldmann U, Hendrickx G, Wint W, Jannin J, Slingenbergh J 2004Tsetse
and trypanosomiasis intervention policies supporting sustainable animal-agricultural
development. J Food Agric Environ 2: 310–314.
15. Lambrecht FL. Trypanosomes and hominid evolution. Bioscience 1985; 35: 640–646.
16. Campbel l MC, Tishkoff SA. The evolution of human genetic and phenotypic variation in Africa.
Curr Biol 2010; 20: R166–R173.
17. Karasik D. Osteoporosis: an evolutionary perspective. Hum Genet 2008; 124: 349–356.
18. Cotter MM, Loomis DA, Simpson SW, Latimer B, Hernandez CJ. Human evolution and
osteoporosis-related spinal fractures. PLoS ONE 2011; 6: e26658.
19. Hassan HY, Underhill PA, Cavalli-Sforza LL, Ibrahim ME. Y-chromosome variation among
sudanese: restricted gene flow, concordance with language, geography, and history. Am J
Phys Anthropol 2008; 137: 316–323.
20. Swallow DM. Genetics of lactase persistence and lactose intolerance. Ann Rev Genet 2003;
37: 197–219.
21. Curry A. The milk revolution: when a single genetic mutation first let ancient Europeans drink
milk, it set the stage for a continental upheaval. Nature 20131500: 20–22.
22. Xu L, Sun H, Zhang X, Wang J ,Sun D, Chen F et al. The -2 2018A allele matches the lactase
persistence phenotype in northern Chinese populations. Scand J Gastroenterol 2010; 45:
168–174.
23. Tishkoff SA, Reed FA, Ranciaro A, Voight BF, Babbitt CC, Silverman JS et al. Convergent
adaptation of human lactase persistence in Africa and Europe. Nat Genet 2006; 39: 31.
24. Ranciaro A, Campbell C, Hirbo J, Ko WY, Froment A, Anagnostou P et al. Genetic
origins of lactase persistence and the spread of pastoralism in Africa. Am J Hum Genet 2014;
94: 499.
25. Bolland MJ, LeungW, Tai V, Bastin S, Gamble GD,Grey A. Calcium intak e and risk of fracture:
systematic review. Br Med J 2015; 351: h4580.
26. Oyoo G.Stemmin g the tide of osteoporosis epidemic in Kenya (Conference Paper), University
of Nairobi, 2010. http://www.kapkenya.org/repository/CPDs/Conferences/Annual.2014/
Osteoporosis%20for%20KOGs%20nyeri.pdf. (Accessed on December 2015).
27. Pollock N, Hamilton B. Osteoporotic fracture in an elite male Kenyan athlete. Br J Sports Med
2007; 42: 10001001.
28. Adebajo AO. Dietary calcium, physical activity, and risk of hip fracture. BMJ 1989; 299:
1165–1165.
29. Gakuu LN. The challenge of fracture management in osteoporotic bones. East African
Orthopaed J 2010; 4:5.
30. Cauley JA, Chalhoub D, Kassem AM, Fuleihan Gel-H. Geographic and ethnic disparities in
osteoporotic fractures. Natl Rev Endocrinol 2014; 10: 338–351.
31. Gupta A. Osteoporosis in India. Natl Med J India 1996; 9: 268–274.
32. Nordin BEC. International patterns of osteoporosis. Clin Orthop Relat Res 1966; 45: 17–30.
33. Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT et al. Prevalence of vitamin D
inadequacy among postmenopausal North American women receiving osteoporosis therapy.
J Clin Endocrinol Metab 2005; 90: 3215–3224.
34. Abelow BJ, Holford TR, Insogna KL. Cross-cultural association between dietary animal
protein and hip fracture: a hypothesis. Calcif Tissue Int 1992; 50: 14–18.
35. Tandon RK, Joshi YK, Singh DS, Narendranathan M, Balakrishnan V, Lal K. Lactose
intolerance in North and South Indians. Am J Clin Nutr 1981; 34: 943–946.
36. Kalkwarf HJ, Zemel BS, Gilsanz V, Lappe JM, Horlick M, Oberfield S et al. The bone mineral
density in childhood study: bone mineral content and density according to age, sex, and race.
J Clin Endocrinol Metab 2007; 92: 2087–2099.
37. Leslie WD. Ethnic differences in bone mass—clinical implications. J Clin Endocrinol Metab
2012; 97: 4331.
38. Tian C, Hinds DA, Shigeta R, Kittles R, Ballinger DG, Seldin MF. A genomewide
single-nucleotide–polymorphism panel with high ancestry information for African American
admixture mapping. Am J Hum Genet 2006; 79: 640–649.
39. Redmond J, Jarjou LMA, Zhou B, Prentice A, Schoenmakers I. Ethnic differences in calcium,
phosphate and bone metabolism. Proc Nutr Soc 2014; 73: 340–351.
40. Prentice A. Diet, nutrition and the prevention of osteoporosis. MRC Human Nutrition
Research. Public Health Nutr 2004; 7: 227.
41. ‘Diagnostic Services,’. The Aga Khan University Hospital, Nairobi (Kenya) hospitals.aku.
edu/Nairobi/ourservices/Pages/AKUHN_Services_Diagnostic.Aspx. (Accessed on December
2015).
42. Kanis JA, Johansson H, Oden A, Cooper C, McCloskey EV. Epidemiology and quality of
life working group of IOF Worldwide uptake of FRAX position paper. Arch Osteoporos 2014;
9: 166.
43. African Journals Online. http://www.ajol.info/index.php (accessed on December 2015).
44. Lemay DG. Milk intake and risk of mortality and fractures in women and men: cohort studies.
Br Med J 2014; 349: g6015.
45. World Bank. GDP per capita, PPP (current international $). World Development
Indicators database (updated on 14 April 2015). http://data.worldbank.org/indicator/
NY.GDP.PCAP.PP.CD (accessed 14 April 2015).
46. Central Intelligence Agency. GDP—per capita (PPP), The World Factbook.
https://www.cia.gov/library/publications/the-world-factbook/rankorder/2004rank.html
(accessed on 7 March 2014).
47. FAO Statistics Division. Milk Consumption—E xcluding Butter (Total) (kg percapita per year),
2011. http://faostat.fao.org/site/610/DesktopDefault.aspx?PageID=610#ancor. (accessed
19 May 2011).
48. FAO. Current Worldwide Annual Meat Consumption per capita, Livestock and Fish Primary
Equivalent, 2013. http://faostat.fao.org/site/610/DesktopDefault.aspx?PageID=610#ancor.
(accessed 31 March 2013).
49. International Monetary Fund. World Economic Outlook Database, October 2015.
https://www.imf.org/external/pubs/ft/weo/2015/02/weodata/index.aspx (accessed 6 October
2015).
50. International Osteoporosis Foundation. Latin America Regional Audit, 2012.
http://www.iofbonehealth.org/data-publications/regional-audits/latin-america-regional-audit
(accessed April 2016).
51. International Osteoporosis Foundation. Asia-Pacific Regional Audit, 2013. http://www.iof-
bonehealth.org/data-publications/regional-audits/asia-pacific-regional-audit. (accessed April
2016).
52. Svedbom A, Hernlund E, Iverga
˚rd M, Compston J, Cooper C, Stenmark J et al. Osteoporosis
in the European Union & a compendium of country-specific reports. Arch Osteoporos 2013;
8: 13.
53. Pinheir o MM, Ciconeli RM, Jacques Nde O. The burden of osteoporosis in Brazil: regional data
from fractures in adult men and women – The Brazilian Osteoporosis Study (BRAZOS). Rev
Bras Reumatol 2010; 50: 113–127.
54. Lix LM, Azimaee M, Osman BA, Caetano P, Morin S, Metge C et al. Public Health.
Osteoporosis-related fracture case definitions for population-based administrative data. BMC
Public Health 2012; 12: 301.
55. Dhanwal DK, Cooper C, Dennison EM. Geographic variation in osteoporotic hip fracture
incidence: the growing importance of Asian influences in coming decades. J Osteoporos
2010; 2010: 757102.
56. Svedbom A, Hernlund E, Iverga
˚rd M. The EU review panel of the International Osteoporosis
Foundation. Osteoporosis in the European Union & a compendium of country-specific reports.
Arch Osteoporos 2013; 8: 44.
57. Svedbom A, Hernlund E, Iverga
˚rd M, Compston J, Cooper C, Stenmark J et al. Osteoporosis
in the European Union & a compendium of country-specific reports. Arch Osteoporos 2013; 8:
60.
58. Svedbom A, Hernlund E, Iverga
˚rd M, Compston J, Cooper C, Stenmark J et al. Osteoporosis
in the European Union & a compendium of country-specific reports. Arch Osteoporos 2013; 8:
69.
59. Svedbom A, Hernlund E, Iverga
˚rd M, Compston J, Cooper C, Stenmark J et al. Osteoporosis
in the European Union & a compendium of country-specific reports. Arch Osteoporos 2013;
8: 76.
60. Dhanwal DK, Dennison EM, Harvey NC. Epidemiology of hip fracture: worldwide geogr aphic
variation. Indian J Orthop 2011; 45:4.
61. Svedbom A, Hernlund E, Iverga
˚rd M. The EU review panel of the International Osteoporosis
Foundation. Osteoporosis in the European Union & a compendium of country-specific reports.
Arch Osteoporos 2013; 8: 92.
62. Siggeir sdottir K, Aspelund T, Jonsson BY, Mogensen B, Gudmundsson EF, Gudnason V et al.
Epidemiology of fractures in Iceland and secular trends in major osteoporotic fractures 1989-
2008. Osteoporos Int 2014; 25: 211–219.
63. Svedbom A, Hernlund E, Iverga
˚rd M. The EU review panel of the International Osteoporosis
Foundation. Osteoporosis in the European Union & a compendium of country-specific reports.
Arch Osteoporos 2013; 8: 101.
64. Fujiwara NK, Marti B, Gutzwiller F. Hip fracture mortality and morbidity in Switzerland and
Japan: a cross-cultural comparison. Soz Praventivmed 1993; 38: 8–14.
65. Azar ES, Abulmajeed S, Masri BK, Kanis JA. The prevalence of osteoporotic hip fractures in
Jordan. Osteoporos Int 2011; 22(Suppl 5): S715.
66. International Osteoporosis Foundation. Eastern European and Central Asia Audit, 2010.
http://www.iofbonehealth.org/eastern-european-central-asian-audit (accessed April 2016).
67. El-Maghraoui A, Ngbanda AR, Bensaoud N. Age-adjusted incidence rates of hip
fractures between 2006 and 2009 in Rabat, Morocco. Osteoporos Int 2013; 24:
1267–1273.
68. Brown P, McNeill R, Rawan E, Willingale J. The burden of osteoporosis in New Zealand:
2007–2020. Osteoporosis New Zealand, Inc., 2007.
High osteoporosis risk among East Africans
CB Hilliard
8JUNE 2016 |www.nature.com/bonekey
69. Emaus N, Olsen LR, Ahmed LA, Balteskard L, Jacobsen BK, Magnus T et al.
Hip fractures in a city in Northern Norway over 15 years: time trends, seasonal
variation and mortality: the Harstad Injury Prevention Study. Osteoporos Int 2011; 22:
2603–2610.
70. Svedbom A, Hernlund E, Iverga
˚rd M. The EU review panel of the International Osteoporosis
Foundation. Osteoporosis in the European Union & a compendium of country-specific reports.
Arch Osteoporos 2013; 8: 164.
71. Lesnyak O, Ershova O, Belova K, Gladkova E, Sinitsina O, Ganert O. The development of a
FRAX model for the Russian Federation. Archives of Osteoporosis Combined data2008-2010
from Yaroslavl and Pervouralsk Olga Yershova, Olga Lesnyak, 2012.
72. Kanis JA, Ode
´n A, McCloskey EV, Johansson H, Wahl D, Cooper C. A systematic review of
hip fracture incidence and probability of fracture worldwide on behalf of the IOF Workin g Group
on Epidemiology and Quality of Life Osteoporosis International. 21 February 2012.
73. Park C, Jang S, Lee A, Kim HY, Lee YB, Kim TY et al. Incidence and mortality after proximal
humerus fractures over 50 years of age in South Korea: National Claim Data from 2008 to
2012. J Bone Metab 2015; 22: 17–21.
74. Svedbom A, Hernlund E, Iverga
˚rd M. The EU review panel of the International Osteoporosis
Foundation. Osteoporosis in the European Union & a compendium of country-specific reports.
Arch Osteoporos 2013; 8: 197.
75. Svedbom A, Hernlund E, Iverga
˚rd M. The EU review panel of the International Osteoporosis
Foundation. Osteoporosis in the European Union & a compendium of country-specific reports.
Arch Osteoporos 2013; 8: 204.
76. Suriyawongpaisal P, Siriwongpairat P, Loahachareonsombat W, Angsachon T, Kumpoo U,
Sujaritputtangkul S et al. A multicenter study on hip fractures in Thailand. J Med Assoc Thai
1994; 77: 488–495.
77. Tuzun S, Eskiyu rtN, Akarirmak U, Saridogan M, Senocak M, Johansson H et al. Incidence of
hip fracture and prevalence of osteoporosis in Turkey: the FRACTURK study. Osteoporos Int
2012; 23: 949–955.
78. Svedbom A, Hernlund E, Iverga
˚rd M. The EU review panel of the International Osteoporosis
Foundation. Osteoporosis in the European Union & a compendium of country-specific reports.
Arch Osteoporos 2013; 8: 212.
79. Gold EB, Crawford SL, Avis NE, Crandall CJ, Matthews KA, Waetjen LE et al. Factors related
to age at natural menopause: longitudinal analyses from SWAN. Am J Epidemiol 2013; 178:
70–83.
80. Riera-Espinoza G. Epidemiology of osteoporosis in Latin America 2008. Salud Publica Mex
2009; 51(Suppl 1): S52–S55.
81. Scrimsh aw NS, Murray E. Lactose tolerance and milk consumption: myths and realities. Arch
Latinoam Nutr 1988; 38: 543–567.
82. Norman Kretchmer, Lactose and Lactase, Scientific American, October, 1972.
83. Koek WN, van Meurs JB, van der Eerden BC, Rivadeneira F, Zillikens MC, Hofman A et al.
The T-13910C polymorphism in the lactase phlorizin hydrolase gene is associated
with differences in serum calcium levels and calcium intake. J Bone Miner Res 2010; 25:
1980–1987.
84. Mattar R, Monteiro MS, Villares CA, Santos AF, Silva JMK, Carrilho FJ. Frequency of LCT-
13910C.T single nucleotide polymorphism associated with adult-type hypolactasia/lactase
persistence among Brazilians of different ethnic groups. Nutr J 2009; 8: 46.
85. Mulcare CA, Weale ME, Jones AL, Connell B, Zeitlyn D, Tarekegn A et al. The allele of a
singlenucleotide polymorphism 13.9 kb upstream of the lactase gene (LCT) (C13.9kbT) does
not predict or cause the lactase-persistence phenotype in Africans. Am J Hum Genet 2004;
74: 1102–1110.
86. Barr SI. Perceived lactose intolerance in adult Canadians: a national survey. Appl Physiol Nutr
Metab 2013; 38: 830–835.
87. Wang YG, Yan YS, Xu JJ, Du RF, Flatz SD, Ku
¨hnau W et al. Prevalence of primary adult
lactose malabsorption in three populations of northern China. Hum Genet. 1984; 67: 103–106.
88. Anne Charlotte Ja
¨ger, "Laktose-intolerans: Gentest for laktose-intolerans - hurtig og billig
diagnostik", DSKB-NYT, no. 2006.
89. Kokkon enJ, Tikkanen S, Savilahti E. Residual intestinal disease after milk allergy in infancy.
J Pediatr Gastroenterol Nutr. 2001; 32: 156–161.
90. De Vrese M, Stegelmann A, Richter B, Fenselau S, Laue C, Schrezenmeir J. Probiotics—
compensation for lactase insufficiency. American Journal of Clinical Nutrition 2001; 73(No. 2):
421S–429s.
91. Bogacs i-Szabo ND, VarkonyiE, Csanyi A, Czibula B, Bede A, Tari O et al. Prevalence of adult-
type hypolactasia as diagnosed with genetic and lactose hydrogen breath tests in Hungarians.
Eur J Clin Nutr 2009; 63: 909–912.
92. Rana SV, Bhasin DK, Naik N. Lactose malabsorption in apparently healthy adults in
northern India, assessed using lactose hydrogen breath test. Indian J Gastroenterol 2004;
23: 78.
93. Cavalli-Sforza LT, Strata A, Barone A, Cucurachi L. Primary adult lactose malabsorption in
Italy: regional differences in prevalence and relationship to lactose intolerance and milk
consumption. Am J Clin Nutr 1987; 45: 748–754.
94. Yoshida Y, Sasaki G, Goto S, Yanagiya S, Takashina K. Studies on the etiology of milk
intolerance in Japanese adults. Gastroenterol Jpn 1975; 10: 29–34.
95. Enattah NS, Jensen TG, Nielsen M, Lewinski R, Kuokkanen M, Rasinpera H et al.
Independent introduction of two lactase-persistence alleles into human populations reflects
different history of adaptation to milk culture. Am J Hum Genet 2008; 82: 57–72.
96. Tishkoff SA, Reed FA, Ranciaro A. Convergent adaptation of human lactase persistence in
Africa and Europe. Nature Genetics 2006; 39: 31–40.
97. Enattah NS, Trudeau A, Pimenoff V, Maiuri L, Auricchio S, Greco L et al. Evidence of
still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans. Am
J Hum Genet 2007; 81: 615–625.
98. Upton J, George P. The prevalence of lactose intolerance (adult hypolactasia) in a randomly
selected New Zealand population. NZMedJ2010; 123: 117–118.
99. Vuorisal o T, Arjamaa O, Vasema
¨gi A, Taavitsainen JP, Tourunen A, Saloniemi I. High lactose
tolerance in North Europeans: a result of migration, not in situ milk consumption. Perspect Biol
Med 2012; 55: 163–174.
100. Coelho M, Luiselli D, Bertorelle G, Lopes AI, Seixas S, Destro-Bisol G et al. Microsatellite
variation and evolution of human lactase persistence. Hum Genet. 2005; 117: 329–339.
101. Torniainen S, Parker MI, Holmberg V, Lahtela E, Dandara C, Jarvela I. Screening of variants
for lactase persistence/non-persistence in populations from South Africa and Ghana. BMC
Genet 2009; 10: 31.
102. Segal I, Gagjee PP, Essop AR, Noormohamed AM. Lactase deficiency in the South African
black population. Am J Clin Nutr 1983; 38: 901–905.
103. Rasinpera
¨H, Forsblom C, Enattah NS, Halonen P, Salo K, Victorzon M et al. The C/C-13910
genotype of adult-type hypolactasia is associated with an increased risk of colorectal cancer in
the Finnish population. Gut 2005; 54: 643–647.
104. Vuorisalo T, Arjam aa O, Vasema
¨gi A, Taavitsainen JP, Tourunen A, Saloniemi I. High lactose
tolerance in North Europeans: a result of migration, not in situ milk consumption. Perspect Biol
Med 2012; 55: 163–174.
105. Nicklas TA, Qu H, Hughes SO, Wagn er S, Foushee H, Shewchuk R et al. Prevalence of self-
reported lactose intolerance in a multi-ethnic sample of adults. Nutr Today 2009; 44: 222–227.
High osteoporosis risk among East Africans
CB Hilliard
BoneKEy Reports |JUNE 2016 9
