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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 r=0.851, with P-value=0.000 in relation to dairy consumption. Lower correlations are seen for hip fracture incidence vis-à-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.
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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
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.
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.
Although sharing similar per capita incomes, and life
expectancies, notable differences in osteoporosis rates exist.
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.
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.
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.
Correspondence: Professor CB Hilliard, Department of History, University of North Texas, P.O. Box 310650, Denton, TX 76203, USA.
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
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%.
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.
However, that number is expected to rise,
and some researchers now suggest that the final count could
number in the thousands.
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.
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
Dairy consumption
Lactase persistence
Animal protein
Per capita
United States 595 253.8 86.5 126.6 54 370
Canada 310.9 206.83 80 108.1 44 967
Europe United
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
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.
See Table 2 for global references on hip fracture incidence per 100,000 per annum.
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.
48 e
International Monetary Fund.
High osteoporosis risk among East Africans
CB Hilliard
2JUNE 2016 |
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
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).
This tsetse-infected area covers nearly one-
third of the African continent or roughly 10 million km
, including
some of the most fertile and best watered regions of
West Africa.
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.
The exception is the trypanotolerant
cattle breeds maintained by Fulbe pastoralists on the margins of
the zone.
Humans, however, show some level of resistance to
all African trypanosome species with the exception of
Trypanosoma brucei gambiense and T. b. rhodesiense.
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.
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
Hong Kong
New Zealand
South Africa
South Korea
United Kingdom
United States
Table 3 References used to compute lactase persistence (LP) single-nucleotide
polymorphisms (as a function of LP ethnic percentages)
(Multiple sources were
Country Citation
Hong Kong Duplicated from China data
Iceland Duplicated from Sweden data
Malta Duplicated from Spain data
New Zealand
South Africa
South Korea Duplicated from China data
United Kingdom
United States
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.
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.
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.
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.
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
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 |
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.
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.
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.
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.
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
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.
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
The second was a 2004 study, ‘Is There Osteo-
porosis in Kenya?’ in which Odawa et al.
reported a diagnosis
of osteoporosis among 24.3% of postmenopausal women and
osteopenia in 32%. In 2010, Dr LN Gakuu
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.
Among pre-menopausal women, the rates were 0.9% and
20.5%, respectively.
The Kenyan rate of osteoporosis for
women 50 years of age and over averaged 243 per 100 000.
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.
A 2-year
project conducted by Zebaze et al.
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.
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.
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.
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
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.
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.
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.
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.
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.
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
zes usin
MINITAB 17, from data
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
High osteoporosis risk among East Africans
CB Hilliard
6JUNE 2016 |
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.
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.
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.
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).
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.
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
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.
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.
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... It has been postulated that TRPV6 sequence variation among populations may have been influenced by domestication of milk-producing animals, beginning $10,000 years ago (27). The dairy farming that swept through Europe, parts of Africa, and much of the rest of the world did not take hold in West Africa due to the tsetse fly, thus calcium consumption in this region remained low ($200-400 mg/day; ref. 28). Surprisingly, West Africans do not develop osteoporosis, as do East Africans and others from dairy farming regions characterized by far higher calcium consumption (29). ...
It is well established that African Americans exhibit higher incidence, higher mortality, and more aggressive forms of some cancers, including those of breast, prostate, colon, stomach, and cervix. Here we examine the ancestral haplotype of the TRPV6 calcium channel as a putative genomic factor in this racial divide. The minor (ancestral) allele frequency is 60% in people of African ancestry, but between 1 and 11% in all other populations. Research on TRPV6 structure/function, its association with specific cancers, and the evolutionary-ecological conditions which impacted selection of its haplotypes are synthesized to provide evidence for TRPV6 as a germline susceptibility locus in cancer. Recently elucidated mechanisms of TRPV6 channel deactivation are discussed in relation to the location of the allele favored in selection, suggesting a reduced capacity to inactivate the channel in those who have the ancestral haplotype. This could result in an excessively high cellular Ca2+, which has been implicated in cancer, for those in settings where calcium intake is far higher than in their ancestral environment. A recent report associating increasing calcium intake with a pattern of increase in aggressive prostate cancer in African-American but not European-American men may be related. If TRPV6 is found to be associated with cancer, further research would be warranted to improve risk assessment and examine interventions with the aim of improving cancer outcomes for people of African ancestry.
... 50 to prevent osteoporosis. However, some observational evidence suggests that increased milk consumption is associated with increased risk and prevalence for fractures, although the components in milk potentially accountable for this elevated risk have not been identified (Michaelsson et al. 2014;Hilliard 2016). One plausible explanation could be related to the pro-inflammatory effects of A1 betacasein protein fraction in milk (Haq, Kapila, Sharma, et al. 2014;Trivedi et al. 2015;Jianqin et al. 2016). ...
Beyond being a source of key nutrients, bovine milk influences physiological functions by synthesising bioactive peptides during the process of digestion. Some of the claimed negative health outcomes associated with milk consumption, such as cardiovascular diseases and type 1 diabetes may be attributed to an opioid peptide, beta-casomorphin-7 (BCM-7), derived from A1 beta-casein. BCM-7 exerts its function by binding to the μ-opioid receptors in the body. It is hypothesised that activation of the μ-opioid receptors in the gut can alter gut microbial composition, impair gut barrier integrity and bile acid metabolism, in addition to increasing gastrointestinal transit time and gut inflammation. Further, it is hypothesised that BCM-7 may influence fractures and obesity via μ-opioid receptor pathways. In conclusion, it appears that BCM-7 might have multiple functions pertinent to human health; however, the evidence is limited and warrants further pre-clinical and clinical studies for hypothesis confirmation.
... Even though 75% of AAs are lactase non-persistent (lactose intolerant), this group still consumes 400% more dietary calcium than its Niger-Kordofanian (NK) West African ancestors. A critical factor that has until now been overlooked is the fact that West Africans are virtually immune to osteoporosis even though their calcium consumption is only 200-400 mg/ day [5]. The calcium homeostatic mechanism is more efficient in this population on account of the TRPV6a variant working in synch with the A563T African variant of the TRPV5 gene, which functions to retain calcium in the body rather than expelling excess amounts in the urine [6]. ...
Full-text available
Cancers identified by the uncontrolled proliferation of the TRPV6 mRNA biomarker, kill African-Americans (AAs) at nearly twice the rate of Whites. Malignancies assigned to this class include: Metastatic prostate cancer, triple negative breast cancer, colorectal and multiple myeloma. This ecological model identifies the cause as an ethnic-specific haplotype of the TRPV6 calcium ion channel, which is also proto-oncogenic. This ancestral TRPV6a variant has been shown in several studies to be more calcium absorbent than the non-African/European TRPV6b allele. AAs inherited strong bones from their low-calcium consuming (200-400 mg/day) Niger-Kordofanian West African ancestors. However, AAs are maladapted to the high calcium (1,000+ mg/day) food environment of the U.S. As a consequence, the ancestral TRPV6a allele can become invasively oncogenic when overexposed to excess free calcium ions, leading to the aforementioned class of cancers.
... people with these ethnic backgrounds, dietary calcium needs might not be nearly as high as people of northern European descent. 384 Given these differences, some have even suggested that dietary recommendations emphasizing dairy consumption are racially biased. 385 Beyond dairy products and fortified dairy alternatives, many other foods are good sources of calcium (with varying bioavailability), including leafy green vegetables ad (e.g., collard greens, kale, broccoli, bok choy, and Brussels sprouts), canned fish with bones, calcium-set tofu, black-eyed peas and white beans, sesame seeds, and almonds. ...
Technical Report
Full-text available
This report distills current research to reveal the human, environmental, and social impacts of the production of high-protein foods other than meat to arm hospitals and other institutions with key information to design the healthiest plate. The findings and associated Purchasing Considerations guide the complex decision-making process encountered when applying an environmental nutrition approach to food purchases, specifically when reducing and replacing meat on the plate.
... This ethnic population has a high bone mineral density and low rate of osteoporosis. Their bone health had been seen as a medical paradox for decades given the fact that their calcium intake was lower than that of Whites [1]. However, in reality they consume 400% more of this mineral than their African genetic ancestors. ...
Full-text available
While I agree that social determinants play an important role in explaining the higher mortality of Black women with triple-negative breast cancer, my research as an evolutionary historian, points to genomics as being an even more pivotal factor. The central actor is the TRPV6 gene, which has an ‘‘ancestral’’ variant carried by Africans and a ‘‘derived’’ haplotype found in Europeans and Asians
Africa is experiencing an exponential increase in the number of older persons. The number of persons surviving with human immunodeficiency virus is simultaneously increasing due to improved availability of anti-retroviral therapy. The burden of non-communicable diseases, in particular, osteoporosis and its consequent fragility fractures, is also predicted to increase. Osteoporosis, however, remains a neglected disease and there are no age-standardized reference data available to accurately screen and diagnose individuals with osteoporosis. Epidemiological studies reporting the incidence of hip fracture or vertebral fractures are limited from Africa, especially Sub-Saharan Africa. The studies are usually limited as they are based on a retrospective data and small study numbers and often from a single study site. However, compared with early initial studies, the more recent studies show that osteoporosis and fractures are increasing across the continent. The overall incidence rates for osteoporosis and fractures still vary greatly between different regions in Africa and ethnic groups. Predisposing factors are similar with those in developed countries, but awareness of osteoporosis is sorely lacking. There is a lack of awareness among the population as well as health authorities, making it extremely difficult to quantify the burden of disease. There is great potential for research into the need and availability of preventive strategies. The FRAX® tool needs to be developed for African populations and may circumvent the shortage of bone densitometry.
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In September 2016, an article in the British Journal of Cancer advised Black females to increase their calcium intake as a means of reducing their susceptibility to the disease. Due to the severity of the cancer among this population and the lack of therapeutic progress in combating it, this research was disseminated widely throughout the United States and given special attention in the African-American media. However, my own work as an applied African historian concludes that Black women should not be encouraged to consume more dietary calcium, as this will increase their risk of ovarian cancer. The reason is that this population carries an ethnic-specific variant of the TRPV6 calcium ion channel (referred to as TRPV6a), which is hypersensitive to carcinogenic-triggering free calcium ions. My work converges with a growing body of research, which identifies free calcium ions in excess of a body's biological setpoint for the mineral triggers metastatic cancers.
Background Studies have shown wide variation in the prevalence of lactose malabsorption across the world, but no systematic reviews or meta-analyses have recently assessed the prevalence of lactose malabsorption in different geographical areas. We aimed to present an updated systematic review and meta-analysis on the prevalence of lactose malabsorption in adults, by countries and regions, and to assess the variation between different testing methods. Methods Studies reporting on prevalence of lactose malabsorption and lactase persistence were identified by searching MEDLINE and Embase from database inception to Nov 2, 2016. We evaluated studies presenting lactose malabsorption or lactase persistence prevalence data in adults and children aged 10 years or older, including cross-sectional and prospective studies, using genotyping, hydrogen breath tests, lactose tolerance tests, and other testing methods. We excluded studies in children younger than 10 years, studies using self-reported data, and studies including inpatients and outpatients at gastroenterological wards. Studies were screened by two authors (CLS and SKF) and data values were extracted by two authors (CLS and SKF) independently. The primary outcome was the prevalence of lactose malabsorption. This study is registered with PROSPERO, number CRD42017064802. Findings We screened 2665 records, and 306 study populations from 116 full-text articles were included (primary sources); data for 144 additional study populations from 59 articles were obtained from review articles, because full-text primary articles could not be obtained (secondary sources). Of the 450 study populations included, 231 were assessed by genotyping, 83 by hydrogen breath tests, 101 by lactose tolerance tests, and 35 by other methods or methods that were not described sufficiently. The studies included 62 910 participants from 89 countries (covering 84% of the world's population). When standardising for country size, the global prevalence estimate of lactose malabsorption was 68% (95% CI 64–72), ranging from 28% (19–37) in western, southern, and northern Europe to 70% (57–83) in the Middle East. When assessing the global prevalence using genotyping data only, the estimate was 74% (69–80), whereas prevalence was 55% (46–65) using lactose tolerance test data, and 57% (46–67) using hydrogen breath test data. Risk of bias was assessed based on ten indicators; 12 of the articles had a score of ten, indicating low risk of bias, 76 had a score of nine, 26 a score of eight, and two articles a score of seven (indicating higher risk of bias). There was substantial heterogeneity between studies within most of the assessed countries. Interpretation Lactose malabsorption is widespread in most of the world, with wide variation between different regions and an overall frequency of around two-thirds of the world's population. Acknowledging regional patterns of lactose malabsorption is important to guide management of gastrointestinal symptoms. Funding None.
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Objective: To examine the evidence underpinning recommendations to increase calcium intake through dietary sources or calcium supplements to prevent fractures. Design: Systematic review of randomised controlled trials and observational studies of calcium intake with fracture as an endpoint. Results from trials were pooled with random effects meta-analyses. Data sources: Ovid Medline, Embase, PubMed, and references from relevant systematic reviews. Initial searches undertaken in July 2013 and updated in September 2014. Eligibility criteria for selecting studies: Randomised controlled trials or cohort studies of dietary calcium, milk or dairy intake, or calcium supplements (with or without vitamin D) with fracture as an outcome and participants aged >50. Results: There were only two eligible randomised controlled trials of dietary sources of calcium (n=262), but 50 reports from 44 cohort studies of relations between dietary calcium (n=37), milk (n=14), or dairy intake (n=8) and fracture outcomes. For dietary calcium, most studies reported no association between calcium intake and fracture (14/22 for total, 17/21 for hip, 7/8 for vertebral, and 5/7 for forearm fracture). For milk (25/28) and dairy intake (11/13), most studies also reported no associations. In 26 randomised controlled trials, calcium supplements reduced the risk of total fracture (20 studies, n=58,573; relative risk 0.89, 95% confidence interval 0.81 to 0.96) and vertebral fracture (12 studies, n=48,967. 0.86, 0.74 to 1.00) but not hip (13 studies, n=56,648; 0.95, 0.76 to 1.18) or forearm fracture (eight studies, n=51,775; 0.96, 0.85 to 1.09). Funnel plot inspection and Egger's regression suggested bias toward calcium supplements in the published data. In randomised controlled trials at lowest risk of bias (four studies, n=44,505), there was no effect on risk of fracture at any site. Results were similar for trials of calcium monotherapy and co-administered calcium and vitamin D. Only one trial in frail elderly women in residential care with low dietary calcium intake and vitamin D concentrations showed significant reductions in risk of fracture. Conclusions: Dietary calcium intake is not associated with risk of fracture, and there is no clinical trial evidence that increasing calcium intake from dietary sources prevents fractures. Evidence that calcium supplements prevent fractures is weak and inconsistent.
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There has been lack of epidemiology of proximal humerus fracture using nationwide database in Asia. The purpose of this study was to investigate the incidence of proximal humerus fracture and its mortality following proximal humerus fracture in Korean over 50 years of age. The Korean National Health Insurance data were evaluated to determine the incidence and mortality of proximal humerus fracture aged 50 years or older from 2008 through 2012. Proximal humerus fracture increased by 40.5% over 5 year of study. The incidence of fracture increased from 104.7/100,000 in 2008 to 124.7/100,000 in 2012 in women and from 45.3/100,000 in 2008 to 52.0/100,000 in 2012 in men, respectively. One year mortality rate after proximal humerus fracture was 8.0% in 2008 and 7.0% in 2012. One year mortality rate were 10.8% for men and 7.0% for women in 2008 and 8.5% for men and 6.4% for women in 2012. Our study showed that the proximal humerus fracture in elderly was recently increasing and associated with high mortality in Korea. Considering proximal humerus fracture was associated with an increased risk of associated fractures and an increased mortality risk, public health strategy to prevent the proximal humerus fracture in elderly will be mandatory.
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Objective To examine whether high milk consumption is associated with mortality and fractures in women and men. Design Cohort studies. Setting Three counties in central Sweden. Participants Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997. Main outcome measure Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture. Results During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker). Conclusions High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.
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Introduction: Osteoporosis is a common disease characterised by low bone mineral density and an increased risk of fragility fractures. Methods: We conducted a literature review of relevant studies relating to the genetics of osteoporosis. Results: Family studies have revealed that bone density and fractures have a strong heritable component but environmental factors also play an important role. This makes identification of the causative genetic variants challenging. Linkage analysis has been successful in identifying the genes responsible for rare inherited diseases associated with abnormalities of bone mass but has been of limited value in osteoporosis. In contrast, genome-wide association studies in large cohort studies have identified 56 loci with robust evidence of association with bone density and 14 loci that predispose to fractures. Although the effect size of the implicated variants is small, many of the loci contain genes known to be involved in regulating bone cell activity through the RANK and Wnt signalling pathways, whereas others contain novel genes not previously implicated in bone metabolism. In a few instances, whole genome and exome sequencing have been successfully used to identify rare variants of large effect size that influence susceptibility to osteoporosis. Conclusion: A future challenge will be to conduct fine mapping and functional analysis of the loci implicated in osteoporosis in order to identify the causal genetic variants and examine the mechanisms by which they influence bone cell function and bone mass. Ultimately this may lead to the identification of biomarkers for susceptibility to osteoporosis and fractures or new therapeutic targets.
Osteoporosis is a major health problem, especially in elderly populations, and is associated with fragility fractures at the hip, spine, and wrist. Hip fracture contributes to both morbidity and mortality in the elderly. The demographics of world populations are set to change, with more elderly living in developing countries, and it has been estimated that by 2050 half of hip fractures will occur in Asia. This review conducted using the PubMed database describes the incidence of hip fracture in different regions of the world and discusses the possible causes of this wide geographic variation. The analysis of data from different studies show a wide geographic variation across the world, with higher hip fracture incidence reported from industrialized countries as compared to developing countries. The highest hip fracture rates are seen in North Europe and the US and lowest in Latin America and Africa. Asian countries such as Kuwait, Iran, China, and Hong Kong show intermediate hip fracture rates. There is also a north-south gradient seen in European studies, and more fractures are seen in the north of the US than in the south. The factors responsible of this variation are population demographics (with more elderly living in countries with higher incidence rates) and the influence of ethnicity, latitude, and environmental factors. The understanding of this changing geographic variation will help policy makers to develop strategies to reduce the burden of hip fractures in developing countries such as India, which will face the brunt of this problem over the coming decades.
Background Osteoporosis is a highly heritable trait. Many candidate genes have been proposed as being involved in regulating bone mineral density (BMD). Few of these findings have been replicated in independent studies.
Objective: To determine the types of fractures encountered in osteoporotic patients and assess the functional outcome of these fractures. Also suggest change of their management and to suggest preventive interventions. Design: A retrospective analytical 10 years study between 1998 and 2007. Setting: The patients were treated at three private hospitals in Nairobi, Kenya. Patients and methods: Consecutive files of traceable patients who were treated for osteoporotic fractures from January 1998 to December 2007. The demographic data, investigations, management methods and functional outcomes of the treatment were determined. The data collected was analysed using SPSS 17.0 windows. Results: Sixty patients were available for review. Forty five were females while 15 were males, giving a F:M ration of 3:1. There were 14 vertebral fractures, 15 hip fractures (5 neck fractures intra-capsular) and 10 extra capsular)., 5 fractures of the distal wrist and 8 humeral fractures, 4 rib fractures, 6 pelvic fractures, 2 sternal fractures and 6 tibial fractures. Twenty six (40%) of the above fractures namely the vertebral, ribs, pelvis and sternum were treated conservatively while 34 fractures (60%) were treated by various methods of internal fixation. All were old patients aged 60 to 101 years (Mean 75 years.) The overall results of the surgery was unsatisfactory in 13(38%) due to metal pull out, screw loosening, periprosthetic fractures, none union seen in patients of hip, humerus, tibia fractures. Twenty one patients (62%) had good outcome. Conclusion: Osteoporotic fractures are a challenge to orthopaedic and trauma surgeons due to unpredictable results of surgery in the elderly patients. Recommendations: It is suggested to make awareness among health workers especially the orthopaedic and trauma surgeons, nurses and physiotherapists so as to put preventive measures in place. As regards operative management careful planning as team work and use of newer techniques, pharmaceuticals like diphosphonates to assist in fracture healing and use of augmentation techniques is worthwhile considering. Kenya Orthopaedic Association (K.O.A) formulate a policy for management of osteoporotic fractures in our local set up. East African Orthopaedic Journal, Vol. 4: March 2010
Osteoporosis is the commonest metabolic bone disease worldwide. The clinical hallmark of osteoporosis is low trauma fracture, with the most devastating being hip fracture, resulting in significant effects on both morbidity and mortality. Data for this review have been gathered from the published literature and from a range of web resources. Genome-wide association studies in the field of osteoporosis have led to the identification of a number of loci associated with both bone mineral density and fracture risk and further increased our understanding of disease. The early strategies for mapping osteoporosis disease genes reported only isolated associations, with replication in independent cohorts proving difficult. Neither candidate gene or linkage studies showed association at genome-wide level of significance. The advent of massive parallel sequencing technologies has proved extremely successful in mapping monogenic diseases and thus leading to the utilization of this new technology in complex disease genetics. The identification of novel genes and pathways will potentially lead to the identification of novel therapeutic options for patients with osteoporosis. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: